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The cracking issue at the bonded interface due to the differing shrinkage performances of newly poured concrete and existing concrete poses a significant threat to the safe service of composite structures. Inspired by the musculoskeletal system, we propose the use of multiscale hybrid reinforced concrete materials, incorporating basalt fiber (BF), polypropylene (PP) fiber, and cellulose nanofiber (CNF), for bridge widening structures. Experimental investigations were carried out to assess the bond splitting tensile strength, diagonal shear strength, crack resistance, development of drying shrinkage deformation, and the propagation behavior of restrained shrinkage-induced cracks in both new and old concrete reinforced with single and hybrid combinations of BF, PP fiber, and CNF. The microstructure, phase composition, and pore structure evolution of BF, PP fiber, and CNF-reinforced concrete were observed and analyzed using scanning electron microscopy, thermogravimetric and derivative thermogravimetric analysis, nuclear magnetic resonance, and mercury intrusion porosimetry. The results indicate that the incorporation of BF, PP fiber, and CNF exhibits excellent synergistic effects, improving the bond and shrinkage performance of the concrete interface. As the CNF content increases, the macro fiber–matrix interface improves. This bio-inspired work will contribute to the development of strong, tough, and sustainable concrete for bridge widening structures.

Abstract Background Human adenovirus (HAdV) is an important pathogen causing acute respiratory infection (ARI) in children. Many countries, including China, have experienced sporadic or outbreaks related to HAdV-4, and death cases were reported. However, there is little research on HAdV-4 and the epidemic situation of HAdV-4 in China is little known. This study was designed to comprehend the prevalence and genetic characteristics of HAdV-4 in ARI children in China. Methods Respiratory tract samples from ARI children hospitalized in six hospitals of Northern and Southern China from 2017 to 2020 were collected for HAdV detection and typing. Clinical information was collected from HAdV-4 positive patients for clinical characteristics and epidemiological analysis. The main capsid proteins and the whole genome sequences were amplified and sequenced for bioinformatics analysis. Results There were 2847 ARI children enrolled, and 156 (5.48%) HAdV positive samples were detected. Eleven HAdV-4 positive samples were identified, accounting for 0.39% of the total samples and 7.05% of the HAdV positive samples. The main manifestations were fever and cough. Two children had conjunctivitis. Two children were diagnosed with severe pneumonia and developed respiratory failure. One of them developed hemophagocytic syndrome and checked in pediatric intensive care unit (PICU). This child had ventricular septal defect. All the children recovered. The isolated strains of HAdV-4 obtained in this study and the reference strains from China located in the same phylogenetic branch (HAdV-4a), while the prototype strain and vaccine strains formed another branch (HAdV-4p). Upon comparison with the prototype strain, there were a few amino acid mutations existing in three major capsid proteins. According to recombination analysis, no new recombination was found. Conclusions The detection rate of HAdV-4 in children hospitalized with ARI was 0.39% in the total samples and 7.05% of all HAdV positive samples. HAdV-4 isolates obtained in this study and other reference strains from China belonged to the HAdV-4a subtype. Our data provided reference for the monitoring, prevention and control of HAdV-4, as well as the research and development of vaccines and drugs.

Abstract The primary impediment to the success of immunotherapy lies in the immune evasion orchestrated by tumors, contributing to the suboptimal overall response rates observed. Despite this recognition, the intricacies of the underlying mechanisms remain incompletely understood. Through preliminary detection of clinical patient tissues, we have found that ALDH1A1 was a key gene for the prognosis of cancer patients and tumor glycolysis. In vitro experiments and tumor formation in nude mice suggested that targeting ALDH1A1 could inhibit tumor growth. Through further analysis of xenograft tumor models in immune-normal mice and flow cytometry, we found that deficiency in ALDH1A1 could promote immune system suppression of tumors in vivo. Specifically, RNA-seq analysis, combined with qPCR and western blot, identified the transcription factor ZBTB7B as downstream of ALDH1A1. The binding sites of the transcription factor ZBTB7B on the LDHA promoter region, which is responsible for regulating the rate-limiting enzyme gene LDHA in glycolysis, were determined using luciferase reporter gene detection and Chip-qPCR, respectively. In addition, the increased SUMOylation of ZBTB7B stabilized its transcriptional activity. Further in vivo and in vitro experiments confirmed that the combination of targeting ALDH1A1 and ZBTB7B with immune checkpoint inhibitors could synergistically inhibit tumors in vivo. Finally, after conducting additional verification of patient tissue and clinical data, we have confirmed the potential translational value of targeting ALDH1A1 and ZBTB7B for tumor immunotherapy. These results emphasize the potential translational significance of targeting ALDH1A1 and ZBTB7B in the realm of tumor immunotherapy. The convergence of ALDH1A1 inhibition and immune checkpoint blockade, particularly with PD-L1/PD-1 mAb, presents a compelling avenue for curtailing tumor immune escape.

Cirriformia species usually inhabit intertidal zones and deep-sea sediments. Their accurate identification has proven to be challenging. Here, we present the complete mitochondrial genome of one Cirriformia tentaculata_Montagu 1808 specimen collected from China. The total length of the complete mitochondrial sequence of C. tentaculata is 15,516 bp and consists of 13 protein-coding genes (PCGs), 23 tRNA genes, two rRNA genes, and an A + T rich region (64.20%). All PCGs begin with the typical ATN start codon, except for cox1, which uses TTG. TAA or TAG serve as termination codons for twelve PCGs, while nad5 terminates with an incomplete codon, T. The phylogenetic tree revealed a close relationship between C. tentaculata in this study, and Cirriformia cf. tentaculata and Timarete posteria from Korea. The information will assist in the future identification and understanding of this species and offers a novel point of reference for identifying Cirriformia species, and phylogenetic studies.

Surface mining is an important way of mining mineral resources. The state and local governments have put forward higher requirements for surface mining in China. Therefore, it is particularly urgent to take surface mining as a science to carry out systematic research, reveal the laws of mining process and phenomenon occurred, and make scientific explanations. First of all, the major technical achievements in the field of surface mining of solid mineral resources in China in the past 40 years were summarized from three aspects: the basic theory of surface mining, the development of key complete sets of equipment and blasting engineering technology. Then, the modern scientific metrology and information metrology technologies were used to conduct a multivariate dynamic analysis of 7128 papers and reports in the past 40 years, and a multi-dimensional quantitative description of the development and evolution process of the main research topics, including the time dimension, was carried out by the cluster analysis. It is found that the evolution of research topics is the result of the coupling effect of many factors, such as technological development, mining status, policy environment, etc. Based on the sorting of the existing major scientific and technological achievements and the objective literature measurement results, it is pointed out that the goal of the future surface mining science is to form a systematic and comprehensive safe, green, efficient and intelligent surface mining technology system, and the realization path is given, that is, to form a hot research topic of surface mining technology system and major equipment, and to strengthen the deep cross integration between the existing hot research and surface mining technology system and major equipment. It also provides some useful suggestions on how to jointly tackle major scientific and technological problems with the advantageous resources of various themes inside and outside the industry to achieve a substantial collaborative innovation among multiple themes. Finally, from the perspective of energy and ecology, the paper looks forward to the development direction of major basic theories and technologies of the future surface mining science from seven aspects: mining area planning theory, intelligent mining design principle, intelligent cluster scheduling theory, safe and efficient mining technology of coal mining in spontaneous combustion prone extra thick coal seams, high slope stability control technology, efficient belt conveyor transportation technology under complex working conditions, and intelligent surface mine system engineering. The development direction of the future surface mining equipment is prospected from five aspects: high efficiency mobile crushing equipment, modular semi-fixed crushing equipment, continuous mining process system equipment, large inclination transportation equipment and large dump machine. It is expected that the study can be used as a reference for scientists and engineers in the surface mining field.

Geographical regions profoundly influence the flavor characteristics of Congou black tea (CBT). In this study, 35 CBT samples from 7 geographical regions were comprehensively characterized by integrated multiple intelligent sensory technologies and untargeted metabolomics analysis. A satisfactory discrimination was achieved through the fusion of multiple intelligent sensory technologies (R2Y = 0.918, Q2 = 0.859). A total of 104 non-volatile and 169 volatile metabolites were identified by UHPLC-HRMS and GC–MS, respectively. Of these, 45 critical differential non-volatile metabolites and 76 pivotal differential volatile metabolites were pinpointed based on variable importance in projection >1 and p

In the present study, the comprehensive quality of Congou black tea (CBT) including aroma, taste, and liquid color was investigated by a combination of gas chromatography electronic nose (GC-E-Nose), electronic tongue (E-tongue), and electronic eye (E-eye). An excellent discrimination of different quality grades of CBT was accomplished through the fusion of GC-E-Nose, E-tongue, and E-eye combined with orthogonal partial least squares discriminant analysis, with parameters of R2Y = 0.803 and Q2 = 0.740. Moreover, the quantitative evaluation of CBT quality was successfully achieved by partial least squares regression analysis, with the absolute error within 1.39 point, and the relative error within 1.62%. Additionally, 12 key variables were screened out by stepwise multiple linear regression analysis, which significantly contributed to the comprehensive quality score of CBT. Our results suggest that the fusion of multiple intelligent sensory technologies offers great potential and practicability in the quality evaluation of black tea.

The park environment is crucial for promoting physical activity (PA). While numerous studies show that park environments influence PA behavior, inconsistencies remain, likely due to varing research methods and parks types. This study employs a fixed spatial grid method to systematically sample four representative parks in Tianjin, China. High-precision orthophoto map (DOM) data from drones provided detailed environmental attributes (like tree canopy area, lawn area, and paved area) and PA characteristics (number of participants, intensity, diversity). The results show: 1) Cluster analysis grouped 1839 park grids into 12 environmental attribute integrations, each correlating with different PA characteristics. “Tree-lined jogging corridors” and “Large sports field areas” exhibit the highest PA intensity, while “Entrance plazas”, “Central plazas,” and “Open sports spaces” have the highest number of participants and PA diversity. 2) Correlation analysis shows that various environmental attributes, including Lawn Area, and Paved Area, are significantly correlated with PA characteristics. 3）Random Forest analysis indicates the key attributes are the paved area for the number of PA participants and PA diversity, and specialized sports facilities area for PA intensity. These findings support urban green space planning and highlight the importance of better park environments for public health.

Abstract In this study, a newly developed composite of biochar-poly(m-phenylenediamine) (BC-PmPD) exhibiting a distinct skeletal structure was synthesized for the purpose of extracting Cr(VI) from aqueous solutions. BC was employed as a supportive carrier onto which PmPD nanoparticles were uniformly affixed through in-situ polymerization and oxidation synthesis, both within and outside the layered configuration of BC. The structural stability and morphologies of BC-PmPD were assessed utilizing Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy, thermogravimetric analysis, analysis of specific surface area and pore size, X-ray photoelectron spectroscopy (XPS), and X-ray diffraction. In comparison to other modified BCs reported, BC-PmPD exhibited the highest Cr(VI) removal rate. Specifically, at 303 K, BC-PmPD achieved a maximum Cr(VI) removal capacity of 775 mg g−1, surpassing the capabilities of unmodified BC and PmPD by 10.4 and 2.13 times, respectively. Analyses involving XPS, FTIR, and density functional theory calculation confirmed that proton transfer happened between protonated amine (−NH2) functional group within the structure of BC-PmPD and HCrO4 − before the formation of hydrogen bond. Subsequently, environmentally persistent free radicals facilitated the reduction of the adsorbed Cr(VI). Quantification of the functional groups indicated that the amino group was responsible for 93.0% of the Cr(VI) adsorption in BC-PmPD. BC-PmPD displayed potent adsorption and reduction capabilities, alongside notable stability, repeatability, and promising potential for application in the remediation for high concentrations of Cr(VI) in electroplating wastewater scenarios. Graphical Abstract

The Dongwuyang Bay of Fujian Province is the core production area for sea cucumber culture in South China; however, research on the environmental status and bacterial community structure in this area is still limited. In this study, we investigated and evaluated the seawater quality in January, which is the peak culture period for sea cucumber in this area, and analyzed the diversity and differential characteristics of seawater and sediment bacterial community structure using the high-throughput sequencing method and analyzed the correlation between environmental factors and bacterial community structure. The following results were obtained: The Makeng eutrophication index reached 21.60, which indicated that this area was experiencing serious eutrophication. Dong´an and Leijiang were experiencing severe eutrophication, and only the Shawan sea area was experiencing moderate eutrophication. The organic pollution assessment showed that Dong´an and Shawan had light organic pollution, while Makeng and Leijiang had moderate organic pollution. A total of 1 520 OTUs were obtained via high-throughput sequencing, belonging to 28 phyla, 57 orders, 163 families, 322 families, and 581 genera. The diversity analysis revealed that the level of bacterial community diversity in the sediment of each region was significantly higher than that of the corresponding seawater diversity and presented stronger spatial heterogeneity. The diversity and abundance in Shawan were the highest. The results of the principal coordinate analysis and similarity analysis showed that there were significant differences in the bacterial community composition between sediment and seawater. The cluster analysis revealed that the cluster was influenced by water exchange and site location. Vibrionaceae, a family with potential pathogenicity, was one of the dominant species in all seawater and sediment samples. LEFSe (line discriminant analysis effect size) analysis of seawater column samples and sediment samples screened 74 specific OTUs (operational taxonomic units) of bacteria at different taxonomic levels. Prediction of gene function and COG (clusters of orthologous groups of proteins) classification statistics showed significant differences in 12 metabolic pathways between seawater and sediment samples (P < 0.05). LEFSe analysis of bacterial community structure from four sites screened 30 specific OTUs at different taxonomic levels. The RDA (redundancy analysis) of the seawater bacterial community structure with environmental factors revealed that temperature, dissolved oxygen, and chlorophyll-a concentration were the major environmental factors affecting the structure in the four sites. Related studies should provide basic data and scientific reference for the management of sea cucumber culture in Fujian Province.

IntroductionRepresentations in working memory can affect distractor suppression in human visual search, and this process is modulated by a separate top-down cognitive control. An increasing body of research has demonstrated that patients with substance use disorder (SUD) have deficits in cognitive control over filtering interference by perceptual distractors. However, their ability to resist proactive interference from working memory has received comparatively less attention.MethodsHere, we investigate this issue by employing a working memory/visual search dual-task paradigm. An intervening gap-location search task was instructed to be performed while participants memorized a written color word, with congruent auditory information present during the memory encoding phase on half of the trials.ResultsResults showed that there was a reliable response time (RT) advantage when the meaning of the memory sample agreed with the color of one of the distractors under the visual alone condition. However, such a result was only found in the control group. More importantly, both groups exhibited comparable facilitation under the audiovisual condition, with the facilitation effect appearing later in the SUD group. Furthermore, the facilitation effect was superior in magnitude and time course under the audiovisual condition to the visual alone condition.DiscussionThese findings highlight how patients with SUD resist distractor interference at the memory level and extend our understanding of how working memory, selective attention, and audiovisual enhancement interact to optimize perceptual decisions in patients with SUD.

ABSTRACT: Avian leukemia virus subgroup J (ALV-J) and chicken infectious anemia virus (CIAV) can be vertically transmitted; however, the pathogenicity of vertically transmitted coinfection with these 2 pathogens has not been studied. In this study, we created a model of chick morbidity in which chicks carried either ALV-J, CIAV, or both viruses via embryo inoculation. Thereafter, we analyzed the effects of vertically transmitted coinfection with CIAV and ALV-J on the pathogenicity of ALV-J and performed a purification assay based on hatching, mortality viremia positivity, and detection of fecal ALV-p27 antigen rates, and body weight. The hatching rate of the ALV-J+CIAV group was 68.57%, lower than those of the single infection and control groups. The survival curve showed that the mortality rates of the CIAV and ALV-J coinfection groups were higher than those of the single infection and control groups. Body weight statistics showed that coinfection aggravated the 7-d growth inhibition effect. The results of ALV-p27 antigen detection in cell culture supernatants showed that the positivity rates of the ALV-J and ALV-J+CIAV groups were 100% at all ages and 0% in the control group. The results of ALV-p27 antigen detection by anal swabs showed that the positivity rates of the ALV-J group were 92.86, 90.90, 88.89, and 93.33% at all ages, and that the ALV-J p27 positivity detection rate of anal swabs was lower than that of plasma virus isolation. The immune organ index of the ALV-J+CIAV group was significantly or very significantly lower than those of the single infection and control groups. The immune organ viral load showed that coinfection with CIAV and ALV-J promoted the proliferation of ALV-J and CIAV in immune organs. Coinfection with ALV-J and CIAV reduced chicken embryo hatchability and increased chick mortality and growth inhibition relative to their respective single infections. Additionally, coinfection with ALV-J + CIAV was even more detrimental in inducing immune organ atrophy (e.g., the thymus, spleen, and bursa), and promoted individual virus replication during coinfection.

Carbazomycins (1–8) are a subgroup of carbazole derivatives that contain oxygen at the C3 and C4 positions and an unusual asymmetric substitution pattern. Several of these compounds exhibit antifungal and antioxidant activities. To date, no systematic biosynthetic studies have been conducted on carbazomycins. In this study, carbazomycins A and B (1 and 2) were isolated from Streptomyces luteosporeus NRRL 2401 using a one-strain-many-compound (OSMAC)-guided natural product mining screen. A biosynthetic gene cluster (BGC) was identified, and possible biosynthetic pathways for 1 and 2 were proposed. The in vivo genetic manipulation of the O-methyltransferase-encoding gene cbzMT proved indispensable for 1 and 2 biosynthesis. Size exclusion chromatography indicated that CbzMT was active as a dimer. In vitro biochemical assays confirmed that CbzMT could repeatedly act on the hydroxyl groups at C3 and C4, producing monomethylated 2 and dimethylated 1. Monomethylated carbazomycin B (2) is not easily methylated; however, CbzMT seemingly prefers the dimethylation of the dihydroxyl substrate (12) to 1, even with a low conversion efficiency. These findings not only improve the understanding of carbazomycin biosynthesis but also expand the inventory of OMT-catalyzing iterative methylations on different acceptor sites, paving the way for engineering biocatalysts to synthesize new active carbazomycin derivatives.

Abstract Objectives This meta-analysis focused on systematically assessing the clinical value of mNGS for infection in hematology patients. Methods We searched for studies that assessed the clinical value of mNGS for infection in hematology patients published in Embase, PubMed, Cochrane Library, Web of Science, and CNKI from inception to August 30, 2023. We compared the detection positive rate of pathogen for mNGS and conventional microbiological tests (CMTs). The diagnostic metrics, antibiotic adjustment rate and treatment effective rate were combined. Results Twenty-two studies with 2325 patients were included. The positive rate of mNGS was higher than that of CMT (blood: 71.64% vs. 24.82%, P

In this study, two kinds of shark repellents, chemical shark repellent and electric pulse shark-repelling device were selected to test their effects on seawater quality as well as the physiology and survival of fish using simulated ecology experiments. Three marine fish species, Japanese flounder (Paralichthys olivaceus), black rockfish (Sebastes schlegelii), and spotted grouper (Oplegnathus punctatus) were selected as test subjects. The results of water quality indicators showed that the chemical shark repellent could significantly reduce the water transparency and pH (P < 0.05), while the electric pulse shark-repelling device had no significant effect. The mortality rate of the fishes under the chemical shark repellent was 100% within 15 min, while it was 0% under both the electric pulse shark-repelling device and the blank control. While investigating the effect of the two repellent methods on the survival and physical activities, the gills and fins of juvenile fish in the chemical shark repellent group were rapidly dyed blue reaching a mortality rate of 100% within 15 min, while the juvenile fish in the electric pulse shark-repelling device group resumed their natural activities rapidly except for exhibiting avoidance behavior when the device was started. The blood indices of the species did not show any significant differences in the chemical shark repellent group because of the acute mortality caused by poisoning. However, in the electric pulse shark-repelling device group, the number of erythrocytes and leukocytes significantly increased in all three fishes. In terms of blood biochemical indices, the chemical shark-repellents caused a significant increase in chloride content, blood glucose, and alkaline phosphatase (AKP) enzyme activity in the juvenile fishes, while the blood albumin content reduced significantly in all three fishes. The use of electric pulse shark-repelling device caused a significant increase in blood glucose and glutamate transaminase activity only in the Japanese flounder. Histopathological results showed that chemical shark repellents caused tissue damage to the gill, liver, spleen, and heart in juvenile fishes. It can be seen that compared to chemical shark repellents, the electric pulse shark-repelling device is a more environmentally friendly way to repel sharks as it has less impact on seawater quality as well as less toxic effects on major marine fishes. These results would provide a scientific basis for the selection of shark repellent methods in ocean exploration activities.

Optimizing water and nitrogen (N) utilization to enhance crop yields under resource constraints is crucial. Straw and its biochar, combined with N fertilizer, are commonly used to improve soil carbon storage and crop growth. However, the effects of straw and N fertilizer management on water consumption, root and shoot characteristics, N uptake, and maize productivity remain unclear. To address this knowledge gap, a three-year (2019–2021) field experiment was conducted in Northwest China. We compared two straw incorporation methods [straw (SI) and straw-derived biochar (BI)] with straw removal (NI) at four N application rates [0 (N0), 225 (N225), 300 (N300), and 375 kg ha–1 (N375)]. Results indicated that compared with NI, both SI and BI significantly increased grain yield (GY), N uptake, and water productivity (WP) (SI < BI; P < 0.05). The maximum GYs were achieved with SIN300 and BIN225, respectively. Notably, compared with SIN300, BIN225 significantly enhanced GY by 10.8% and 5.8% and improved WP by 19.2% and 9.9% (P < 0.05). This improvement was mainly attributed to the increased water consumption after tasseling and crop transpiration (T) in evapotranspiration (ET). Furthermore, N application resulted in increased root distribution in shallow soil layers (0–0.3 m). Under BIN225, roots exhibited a longer, thinner and deeper profile, minimizing root redundancy and enhancing root efficiency in water and N absorption during the reproductive stage of maize. In contrast, SIN300 resulted in shorter, thicker, and shallower roots, leading to a reduced shoot-root ratio of 12.2% (P < 0.05). Based on the normalization and fitting curves, BI combined with reduced N (240 kg ha–1) improved WP by 24.5%, achieving 98.7% of the maximum GY for drip-irrigated maize (16.98 Mg kg–1). Overall, these findings provide a novel straw strategy for sustainable field management in arid irrigation agriculture and similar ecosystems.

The coronavirus disease 2019 (COVID-19) pandemic caused by frequently mutating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a worldwide impact. However, detailed data on the potential aerosol transmission of SARS-CoV-2 in real-world and controlled laboratory settings remain sparse. During the COVID-19 pandemic in Shanghai, China in 2022, samples were collected in a Fangcang shelter hospital, a large-scale temporary hospital rapidly built by converting the existing National Exhibition and Convention Center (Shanghai) into a health care facility. Aerosol samples at different sites and intervals around patients and in public areas, surface samples, and pharyngeal swab samples from corresponding patients were included. Samples were tested for SARS-CoV-2 using real-time quantitative polymerase chain reaction (RT-qPCR) assays, followed by sequencing if the cycle threshold (Ct) value was < 30. The positivity rate for SARS-CoV-2 in aerosol samples was high in contaminated zones (37.5%, 104/277), especially around the bed (41.2%, 68/165) and near ventilation inlets (45.2%, 14/31). The prevalence of SARS-CoV-2 around the bed, public areas, and air inlets of exhaust vents fluctuated and was closely related to the positivity rate among patients at corresponding sampling sites. Some surface samples of different personal protective equipment from medical staff had high positivity rates. Sixty sequences of joined ORF1ab and spike genes obtained from sixty samples represented two main clusters of Omicron SARS-CoV-2. There was consistency in virus sequences from the same patient and their environment, and the detected virus sequences matched those of virus strains in circulation during the collection periods, which indicated a high likelihood of cross-contamination in the Fangcang shelter hospital. In summary, the results provide a quantitative and real landscape of the aerosol transmission of SARS-CoV-2 and a patient-centered view of contamination in large and enclosed spaces and offer a useful guide for taking targeted measures to avoid nosocomial infections during the management of SARS-CoV-2 or other respiratory virus diseases in a Fangcang shelter hospital.

Cold stress causes considerable damage to tender tea seedlings. Previous studies have explored changes in the physiological and biochemical factors of tea in response to cold stress; however, the mechanisms of cold resistance in ancient tea tree plants are unclear. The aim of this study was to analyze the effects of 0 °C cold stress for 15 days and 24 °C ambient temperature recovery for 5 days on the physiological and biochemical characteristics of two representative old tea varieties: Dali tea and Siqiu tea. The results revealed significant changes in antioxidant, photosynthetic efficiency, and physiological and biochemical indicators in response to cold stress, with the two species exhibiting different patterns. Cold stress decreased chlorophyll and carotene content, Fv/Fm, Y(II), non-photochemical quenching coefficient, photochemical quenching, and superoxide dismutase (SOD) activity, and increased intercellular CO2 concentration and ascorbate peroxidase activity. Siqiu tea showed a higher increase in soluble sugar content and antioxidant enzyme activity and a lower accumulation of malondialdehyde and minimal fluorescence (F0) than Dali, indicating a greater tolerance to cold stress. Based on partial least-squares discriminant analysis, six key differential physiological indicators of cold resistance—water-soluble sugar, F0, peroxidase, catalase, SOD, and gas conductance—were identified. Our findings provide technical support for identifying ways to protect ancient tea trees from extreme weather conditions.

Ga2O3, with its large band gap, is a promising material suitable for utilization in solar-blind photodetection. Sapphire with a higher lattice match with Ga2O3 was used as the substrate for epitaxial growth of Ga2O3. Here, the epitaxial layers of Ga2O3 were deposited by MOCVD on patterned sapphire substrates. The structure of epitaxial Ga2O3 layers on patterned substrates has been identified by X-ray diffractometry. To investigate the influence of the patterned substrates on the formation of epitaxial layers, thin Ga2O3 layers were grown on a flat sapphire substrate under the same conditions. Both types of samples were β-phase. However, no improvement in the layers’ crystalline quality was discovered when utilizing patterned sapphire substrates. In addition, the performance of the obtained two types of Ga2O3 photodetectors was compared. The photoelectric properties, such as responsivity, response speed, and detection capability, were different in the case of flat samples.

1,4-diaminobutane is widely used in the industrial production of polymers, pharmaceuticals, agrochemicals and surfactants. Owing to economic and environmental concerns, there has been a growing interest in using microbes to produce 1,4-diaminobutane. However, there is lack of research on the influence of cofactors pyridoxal phosphate (PLP) and NADPH on the synthesis of 1,4-diaminobutane. PLP serves as a cofactor of ornithine decarboxylase in the synthesis of 1,4-diaminobutane. Additionally, the synthesis of 1 mol 1,4-diaminobutane requires 2 mol NADPH, thus necessitating consideration of NADPH balance in the efficient synthesis of 1,4-diaminobutane by Escherichia coli. The aim of this study was to enhance the synthesis efficiency of 1,4-diaminobutane through increasing production of PLP and NADPH. By optimizing the expression of the genes associated with synthesis of PLP and NADPH in E. coli, cellular PLP and NADPH levels increased, and the yield of 1,4-diaminobutane also increased accordingly. Ultimately, using glucose as the primary carbon source, the yield of 1,4-diaminobutane in the recombinant strain NAP19 reached 272 mg/L·DCW, by increased 79% compared with its chassis strain.

Abstract Drought is a most prevalent environmental stress affecting the productivity of rainfed wheat and maize in the semiarid Loess Plateau of China. Sustainable agricultural practices such as intercropping are important for enhancing crop performance in terms of better physiological and biochemical characteristics under drought conditions. Enzymatic and non-enzymatic antioxidant enzyme activities are associated with improved abiotic tolerance in crop plants, however, its molecular mechanism remains obscure. A 2-year field study was conducted to evaluate the influence of intercropping treatment viz. wheat mono-crop (WMC), maize mono-crop (MMC), intercropping maize (IM) and wheat (IW) crops, and nitrogen (N) application rates viz. control and full-dose of N (basal application at 150 and 235 kg ha−1 for wheat and maize, respectively) on chlorophyll fluorescence, gas exchange traits, lipid peroxidation, antioxidative properties and expression patterns of six tolerance genes in both crops under rainfed conditions. As compared with their respective monocropping treatments, IW and IM increased the Fo/Fm by 18.35 and 14.33%, PS-11 efficiency by 7.90 and 13.44%, photosynthesis by 14.31 and 23.97%, C-capacity by 32.05 and 12.92%, and stomatal conductance by 41.40 and 89.95% under without- and with-N application, respectively. The reductions in instantaneous- and intrinsic-water use efficiency and MDA content in the range of 8.76–26.30% were recorded for IW and IM treatments compared with WMC and MMC, respectively. Compared with the WMC and MMC, IW and IM also triggered better antioxidant activities under both N rates. Moreover, we also noted that intercropping and N addition regulated the transcript levels of six genes encoding non-enzymatic antioxidants cycle enzymes. The better performance of intercropping treatments i.e., IW and IM were also associated with improved osmolytes accumulation under rainfed conditions. As compared with control, N addition significantly improved the chlorophyll fluorescence, gas exchange traits, lipid peroxidation, and antioxidant enzyme activities under all intercropping treatments. Our results increase our understanding of the physiological, biochemical, and molecular mechanisms of intercropping-induced water stress tolerance in wheat and maize crops.

Abstract Background There is no standard first‐line immunochemotherapy regimen for transplant‐ineligible patients with mantle cell lymphoma (MCL) currently, and the efficacy of various treatment remains unclear. Methods We conducted a Bayesian network meta‐analysis (NMA) of all eligible randomized controlled trials. Pairwise comparisons and ranking of different first‐line treatment options were performed. Results Nine studies were included in the NMA, involving a total of 2897 MCL patients. The BR‐Ibrutinib+R regimen showed the best progression‐free survival (PFS), with a surface under the cumulative ranking curve (SUCRA) of 0.89 and probability of being the best treatment (PbBT) of 69%. The VR‐CAP regimen was the most potential intervention to improve overall survival (OS), with a SUCRA of 0.89 and PbBT of 63%. Compared with the R‐CHOP regimen, the BR regimen achieved a better PFS (hazard ratio [HR] 0.45 [95% credible interval 0.2–0.96]). The BR‐Ibrutinib+R regimen (HR 0.14 [0.02–0.99]), BR+R regimen (HR 0.19 [0.034–0.99]), and BR regimen (HR 0.3 [0.08–1.03]) were superior to CHOP regimen with better PFS. The R‐FC regimen (HR 2.27 [1.01–5.21]) or FC regimen (HR 3.17 [1.15–8.71]) was inferior to the VR‐CAP regimen with a worse OS. Conclusions Our study presents the most promising first‐line treatment strategy for transplant‐ineligible MCL patients in terms of PFS and OS, which provides innovative treatment strategy for MCL treatment.

In recent years, continuous high temperature and marine heat waves in summer have become major limitations for the sustainable development of sea cucumber aquaculture. In 2019, our team invented a cooling equipment based on cooled atomization air, which can reduce the water temperature of the culture pond in summer. Previous tests showed that the survival rates of the sea cucumbers in the equipped ponds were higher than the unequipped ponds during the high temperature. In this study, five equipped ponds were selected as experimental groups (groups E1 and E2 were labeled according to their geographic location) and three unequipped ponds were selected as control groups (labeled group C), then the water quality, sedimental quality, and the sedimental microbial community structure of the eight ponds were analyzed in order to reveal the mechanism of the higher survival rate using the cooling equipment. The results showed that the temperature of the bottom water of the two experimental groups was significantly lower than that of the control group (P < 0.05). The dissolved oxygen (DO) level in the bottom water of the experimental groups was significantly higher than that of the control group (P < 0.05). Both the ammonia nitrogen concentration in the bottom water and the concentrations of nitrite nitrogen, and chemical oxygen demand (COD) and ammonia nitrogen in pond sediments of the two experimental groups were significantly lower than that of the control group (P < 0.05). The sedimental microbial community structure of all the ponds was also investigated, and the OTUs (optical transform units) were numbered from 707 to 808. Alpha diversity analysis showed that the abundance and diversity of the experimental group were higher than those of the control group. PCoA (principal coordinates analysis) showed that the bacterial composition and community structure among the two experimental groups were more similar, while there were significant differences between the experimental and the control groups. The species distribution analysis on the order level showed that the similarity between the two experimental groups is higher than that between the experimental and control groups. The relative abundance of Rhizobiales, Lactobacillales, and Micrococcineae in the experimental groups were significantly higher than that in the control groups. Thirteen OTUs with significant differences among three groups were selected using LEfSe (LDA effect size) analysis. The correlation analysis between microbial community structure and environmental factors showed that the abundance of microbial species involved in the nitrogen cycle was significantly higher in the experimental groups than that of the control groups. Then OTU7, OTU29 and OTU108 were screened and significant correlation was found with ammonia nitrogen concentration in all of the tested ponds, and they are classified as Ochrobactrum, Escherichia-Shigella and Bacillus, respectively. In the 25 predicted COG (clusters of orthologous groups of proteins) metabolic pathways in prokaryotes, 18 metabolic pathways exhibited significant differences (P < 0.05) between the experimental groups and the control groups. All the results indicated that the use of the equipment could significantly improve the pond water quality and sediment environment, and positively affect the sedimental microbial community structure of the bottom water. The results of this study would provide scientific support for the popularization and application of the equipment.

BackgroundCerebral small vessel disease (CSVD) attaches people’s attention in recent years. In this study, we aim to explore retinal structure and vessel density changes in CSVD patients.MethodsWe collected information on retinal metrics assessed by optical coherence tomography (OCT) and OCT angiography and CSVD characters. Logistic and liner regression was used to analyze the relationship between retinal metrics and CSVD.ResultsVessel density of superficial retinal capillary plexus (SRCP), foveal density- 300 length (FD-300), radial peripapillary capillary (RPC) and thickness of retina were significantly lower in CSVD patients, the difference only existed in the thickness of retina after adjusted relevant risk factors (OR (95% CI): 0.954 (0.912, 0.997), p = 0.037). SRCP vessel density showed a significant downward trend with the increase of CSVD scores (β: −0.087, 95%CI: −0.166, −0.008, p = 0.031). SRCP and FD-300 were significantly lower in patients with lacunar infarctions and white matter hypertensions separately [OR (95% CI): 0.857 (0.736, 0.998), p = 0.047 and OR (95% CI): 0.636 (0.434, 0.932), p = 0.020, separately].ConclusionSRCP, FD-300 and thickness of retina were associated with the occurrence and severity of total CSVD scores and its different radiological manifestations. Exploring CSVD by observing alterations in retinal metrics has become an optional research direction in future.

IntroductionMetagenomic next-generation sequencing (mNGS) is a novel technique for detecting pathogens. This retrospective study evaluated the diagnostic value of mNGS using plasma for infections in hematology patients and its impact on clinical treatment and prognosis in different subgroups of hematology patients.MethodsA total of 153 hematology patients with suspected infection who underwent mNGS using plasma were enrolled in the study. Their clinical histories, conventional microbiological test (CMT) results, mNGS results, treatment and prognosis were retrospectively analyzed.ResultsIn 153 plasma samples, mNGS yielded a higher positivity rate than CMT (total: 88.24% vs. 40.52%, P 0.05; mortality rate: 29.17% vs. 29.63%, P > 0.05) with more aggressive antibiotic adjustments (45.83% vs. 22.22%, P < 0.01).ConclusionmNGS can detect more microorganisms with higher positive rates, especially in patients with neutropenia. mNGS had better clinical value in patients with hematopoietic stem cell transplantation (HSCT) or neutropenia, which had a positive effect on treatment and prognosis.

In recent years, there has been increased interest in multispectral pedestrian detection using visible and infrared image pairs. This is due to the complementary visual information provided by these modalities, which enhances the robustness and reliability of pedestrian detection systems. However, current research in multispectral pedestrian detection faces the challenge of effectively integrating different modalities to reduce miss rates in the system. This article presents an improved method for multispectral pedestrian detection. The method utilises a saliency detection technique to modify the infrared image and obtain an infrared-enhanced map with clear pedestrian features. Subsequently, a multiscale image features fusion network is designed to efficiently fuse visible and IR-enhanced maps. Finally, the fusion network is supervised by three loss functions for illumination perception, light intensity, and texture information in conjunction with the light perception sub-network. The experimental results demonstrate that the proposed method improves the logarithmic mean miss rate for the three main subgroups (all day, day and night) to 3.12%, 3.06%, and 4.13% respectively, at “reasonable” settings. This is an improvement over the traditional method, which achieved rates of 3.11%, 2.77%, and 2.56% respectively, thus demonstrating the effectiveness of the proposed method.

Long-term fertilization management is not only an important source of nutrients to ensure food productivity, but also significantly affects soil organic carbon (SOC) and total nitrogen (TN) sequestration in agroecosystems, as well as strongly affects soil aggregate structure and microbiological characteristics. Straw incorporation is expected to promote SOC and TN. However, how long-term fertilization managements change soil aggregate distribution, SOC and TN components, and microbiological characteristics in straw-returned dryland fields are unknown, and how the quantitative analysis of the relationship between SOC and TN and biological factors, as well as their relative importance at an aggregate scale, are equally unknown. In addition, whether fertilization management can achieve higher crop productivity and economic efficiency while achieving higher soil carbon and nitrogen sequestration is a topic of greater concern to farmers. A 10-year in situ field fertilization experiment with five N application rates (0, 75, 150, 225, and 300 kg·N·ha−1, denoted as N0, N75, N150, 225, and N300, respectively) was conducted on straw-returned dryland. The wet sieving method was used to investigate the soil aggregates distribution in aggregate fractions (>5, 5–2, 2–1, 1–0.5, 0.5–0.25, and 0.25 mm) and mean weight diameter. Then, K2CrO7-H2SO4 oxidation and Kjeldahl digestion methods were used to determine the SOC and TN contents and calculate the contributing rate of aggregate size fractions in SOC and TN. It was found that most SOC and TN are distributed in macro-aggregate (especially 2–1 mm). N225 significantly increased the SOC and TN in bulk soil and aggregate scale, especially the macro-aggregate contribution rate to SOC and TN. At the same time, chloroform fumigation extraction and the 3, 5-dinitrosalicylic acid method were adopted for the determination of soil microbial biomass and enzyme activity. It was found that microbial activity characteristics were consistent with SOC and TN dynamics at bulk soil and aggregate scales. Through further variation partitioning analysis demonstrated microbial biomass and enzyme activities accounting for 26 % and 34 % of the variation in SOC and TN. Finally, by calculating economic benefits, N225 maximizes crop yield and economic efficiency. Overall, reduced N application rate (N225) improves the soil's bioactive functioning, promotes carbon and nitrogen sequestration by promoting aggregation and improving the microbial biomass and enzyme activities in macro-aggregates, as well as enhancing crop yields and maximizing economic benefits in straw-returned dryland fields. These results would provide new insights into fertilization management strategies for improving soil conditions in terms of optimizing the interaction of soil aggregate structure–microbial activity characteristics–SOC and TN sequestration, as well as achieving sustainable agricultural development in straw-returned dryland fields.

Shaking is an innovative technology employed in black tea processing to enhance flavor. However, the effects of shaking on the evolutionary mechanisms of volatile metabolites (VMs) remain unclear. In this study, we compared the effects of a shaking–withering method with those of traditional withering on the flavor and VMs transformation of black tea. The results showed that black tea treated with shaking exhibited excellent quality with floral and fruity aroma. Based on gas chromatography-tandem mass spectrometry, 128 VMs (eight categories) were detected. Combining variable importance projection with odor activity value analysis, eight key differential VMs were identified. Shaking could promote the oxidative degradation of fatty acids and carotenoids and modulate the biosynthesis of terpenoids to facilitate the formation of floral/fruity VMs (such as (Z)-hexanoic acid-3-hexenyl ester, ethyl hexanoate, trans-β-ionone, and decanal). Our findings provide theoretical guidance for the production of high-quality black tea with floral and fruity aromas.

microRNAs (miRNAs), involved in post-transcriptional gene regulation, play important roles in the growth, development, cell differentiation, and immune defense of eukaryotes. Apostichopus japonicus has become an economically important species for marine aquaculture in China; however, the outbreak of diseases, such as skin ulcer syndrome (SUS), has led to great losses in aquaculture development. Therefore, molecular mechanisms underlying disease occurrence must be further elucidated. In the present study, Vibrio splendidus, an important causative pathogen of SUS, was used as the stress strain (1×106 CFU/mL) in an artificial infection experiment. Body wall of the diseased (PT16S) and healthy (PT10H) samples was subjected to miRNA-Seq. Differentially expressed miRNAs (DEmiRNAs) were screened using bioinformatics. The target genes of DEmiRNAs were predicted and used for constructing miRNA-mRNA regulatory networks. Through miRNA-Seq, respectively 5 902 588 and 5 053 529 valid reads were generated for the PT10H and PT16S samples. A total of 13 DEmiRNAs (P≤0.05) were screened between PT10H and PT16S, of which two were upregulated and 11 downregulated. Target gene prediction revealed that the two upregulated DEmiRNAs bound to 3010 target genes, which were annotated to 585 GO terms and 24 signaling pathways (P≤0.05), while the 11 downregulated DEmiRNAs bound to 19 072 target genes, which were annotated to 514 GO terms and 22 signaling pathways (P≤0.05). In the validation test, the consistency rate of the sequencing and qRT-PCR data reached 70%. Two immune-related pathways (ubiquitin-mediated proteolysis and Notch signaling) were selected and used to construct the miRNA-mRNA regulatory networks. The 13 DEmiRNAs could bind 134 ubiquitin-mediated proteolytic mRNAs and 109 Notch signaling mRNAs. Specifically, Aja-miR-1559-3p, Aja-miR-7550-5p, Aja-miR-2478, and Aja-miR-9277-3p may be involved in the regulation of ubiquitin-mediated proteolysis and Notch signaling. Our results provide primary data for understanding the post-transcriptional regulatory mechanisms of diseases in sea cucumber.

IntroductionPine wilt disease (PWD) is responsible for extensive economic and ecological damage to Pinus spp. forests and plantations worldwide. PWD is caused by the pine wood nematode (PWN, Bursaphelenchus xylophilus) and transmitted into pine trees by a vector insect, the Japanese pine sawyer (JPS, Monochamus alternatus). Host infection by PWN will attract JPS to spawn, which leads to the co-existence of PWN and JPS within the host tree, an essential precondition for PWD outbreaks. Through the action of their metabolites, microbes can manipulate the co-existence of PWN and JPS, but our understanding on how key microorganisms engage in this process remains limited, which severely hinders the exploration and utilization of promising microbial resources in the prevention and control of PWD.MethodsIn this study we investigated how the PWN-associated fungus Aspergillus promotes the co-existence of PWN and JPS in the host trees (Pinus massoniana) via its secondary metabolite, sterigmatocystin (ST), by taking a multi-omics approach (phenomics, transcriptomics, microbiome, and metabolomics).ResultsWe found that Aspergillus was able to promote PWN invasion and pathogenicity by increasing ST biosynthesis in the host plant, mainly by suppressing the accumulation of ROS (reactive oxygen species) in plant tissues that could counter PWN. Further, ST accumulation triggered the biosynthesis of VOC (volatile organic compounds) that attracts JPS and drives the coexistence of PWN and JPS in the host plant, thereby encouraging the local transmission of PWD. Meanwhile, we show that application of an Aspergillus inhibitor (chiricanine A treatment) results in the absence of Aspergillus and decreases the in vivo ST amount, thereby sharply restricting the PWN development in host. This further proved that Aspergillus is vital and sufficient for promoting PWD transmission.DiscussionAltogether, these results document, for the first time, how the function of Aspergillus and its metabolite ST is involved in the entire PWD transmission chain, in addition to providing a novel and long-term effective nematicide for better PWD control in the field.

Despite the importance of fixation in determining green tea quality, its role in reducing the bitter and astringent taste of this beverage remains largely unknown. Herein, an electromagnetic roller-hot-air–steam triple-coupled fixation (ERHSF) device was developed, and its operating parameters were optimized (steam volume: 20 kg/h; hot-air temperature: 90 °C; hot-air blower speed: 1200 r/min). Compared with conventional fixation treated samples, the ratio of tea polyphenols to free amino acids and ester-catechins to simple-catechins in ERHSF-treated samples was reduced by 11.0% and 3.2%, reducing bitterness and astringency of green tea; amino acids, soluble sugars, and chlorophyll contents were significantly increased, enhancing the freshness, sweetness, and greenness; the color indexes, such as L/L* value of brightness and -a/-a* value of greenness, were also improved, and ERHSF-treated samples had the highest sensory scores. These results provided theoretical support and technical guidance for precise quality improvement of summer-autumn green tea.

Trust plays an important role in the human economy and people’s social lives. Trust is affected by various factors and is related to many brain regions, such as the dorsolateral prefrontal cortex (DLPFC). However, few studies have focused on the impact of the DLPFC on trust through transcranial direct current stimulation (tDCS), although abundant psychology and neuroscience studies have theoretically discussed the possible link between DLPFC activity and trust. In the present study, we aimed to provide evidence of a causal relationship between the rDLPFC and trust behavior by conducting multiple rounds of the classical trust game and applying tDCS over the rDLPFC. We found that overall, anodal stimulation increased trust compared with cathodal stimulation and sham stimulation, while the results in different stages were not completely the same. Our work indicates a causal relationship between rDLPFC excitability and trust behavior and provides a new direction for future research.

Two-terminal artificial optoelectronic devices in which photoexcited carriers and ions are coupled constitute a built-in artificial neural network that can sense, memory and process simultaneously.

Feature selection (FS) is an important way to achieve high-precision and efficient classification of hyperspectral remote sensing images. However, most existing FS methods use a fixed scale to extract features and the relationship between spatial and spectral dimensions is ignored. In fact, this correlation is useful for classification. In this article, a multiscale feature fusion network based on global weighting (MSFGW) is proposed in which a global weighting mechanism is explored to catch spatial–spectral information at multiple scales. First, the multiscale feature extraction module composed of group convolution and dilated convolution is utilized to extract the multiscale features. With the increase of the dilation rate, the module takes the spatial differences at varying scales. Second, a 3-D weighting mechanism is used to combine the spatial and spectral correlated information for reducing the interference of homologous and heterologous and boosting the feature discrimination ability. Then, multiscale weighted features are fused to integrate the internal information of all bands at different scales. Finally, the band reconstruction network is used to select representative bands according to their entropy. The experimental results with the state-of-the-art FS algorithms on four widely hyperspectral datasets demonstrate that the features selected by MSFGW have obvious advantages in classification with only a few training samples.

Abstract Objective Our study aimed to investigate the association between the subarachnoid extension of intracranial hemorrhage (SAHE) and clinical outcomes in patients with supratentorial intracerebral hemorrhage (ICH). Methods We analyzed the data from a prospective, multi-center, and registry-based database. Two experienced investigators independently assessed ICH imaging data. We compared baseline characteristics and follow-up outcomes. Multivariable logistic regression analysis was used to evaluate the association between SAHE and poor clinical outcomes. We also performed Kaplan–Meier curves and Cox proportional hazards regression analyses to analyze whether SAHE was relevant to a higher mortality rate. Results A total of 931 patients were included in this study (SAHE vs. no SAHE, 121 [13.0%] vs. 810 [87.0%]). Patients with SAHE had more severe neurological deficits, higher scores of the mRS, and more remarkable mortality rates at follow-up (all p values

Abstract Severe muscle injury is hard to heal and always results in a poor prognosis. Recent studies found that extracellular vesicle-based therapy has promising prospects for regeneration medicine, however, whether extracellular vesicles have therapeutic effects on severe muscle injury is still unknown. Herein, we extracted apoptotic extracellular vesicles derived from mesenchymal stem cells (MSCs-ApoEVs) to treat cardiotoxin induced tibialis anterior (TA) injury and found that MSCs-ApoEVs promoted muscles regeneration and increased the proportion of multinucleated cells. Besides that, we also found that apoptosis was synchronized during myoblasts fusion and MSCs-ApoEVs promoted the apoptosis ratio as well as the fusion index of myoblasts. Furthermore, we revealed that MSCs-ApoEVs increased the relative level of creatine during myoblasts fusion, which was released via activated Pannexin 1 channel. Moreover, we also found that activated Pannexin 1 channel was highly expressed on the membrane of myoblasts-derived ApoEVs (Myo-ApoEVs) instead of apoptotic myoblasts, and creatine was the pivotal metabolite involved in myoblasts fusion. Collectively, our findings firstly revealed that MSCs-ApoEVs can promote muscle regeneration and elucidated that the new function of ApoEVs as passing inter-cell messages through releasing metabolites from activated Pannexin 1 channel, which will provide new evidence for extracellular vesicles-based therapy as well as improving the understanding of new functions of extracellular vesicles.

Endometrial cancer (EC) is a gynecological malignant tumor characterized by high incidence. EC occurrence and development are regulated by numerous molecules and signal pathways. There is a need to explore key regulatory molecules to identify potential therapeutic targets to reduce the incidence of EC. Treatment by targeting a single molecule is characterized by poor efficacy owing to the development of resistance and significant side effects. The current study explored potential candidates in EC by integrating bioinformatics analysis and in vivo and in vitro experimental validation to circumvent the limitation of low efficacy of currently used molecules. Molecular dynamics simulations provide details at the molecular level of intermolecular regulation. In the current study, MLLT11 and TRIL were identified as important regulatory molecules in EC. The two molecules formed a heteromultimer by binding to AKT protein, which induced its phosphorylation of threonine at position 308. Ultimately, the complex stimulates PI3K/AKT/mTOR signaling pathway, a pivotal pathway in tumors. The findings of the current study show a novel complex, MLLT11-TRIL, which can act as AKT protein agonist, thus inducing activity of PI3K/AKT/mTOR signaling pathway. Targeting MLLT11 and TRIL simultaneously, or blocking the formation of the MLLT11-TRIL complex, can abrogate progression of EC.

This paper aimed to explore the biochemical characteristics of fresh leaf raw materials of large-leaf cultivars. In this study, four different tenderness fresh tea leaves of single bud, one bud with one leaf, one bud with two leaves and one bud with three leaves picked from Yunnan large-leaf cultivars (Qingshui No.3, Xianggui Yinhao, Yunkang No.10, Yunkang No.14, Yuncha Purui) were selected as the research objects. The variation of raw material taste quality with tenderness of different varieties of Yunnan large-leaf cultivars was investigated by detecting the content of its main flavor substances (tea polyphenols, flavonoids, amino acids and soluble sugars, etc.). Multivariate statistical methods were used to explore the categories and key differential indexes of fresh leaves with different tenderness, meanwhile, fisher discriminant analysis was used to establish the discriminant models for different types of fresh leaves. The results showed that the higher the maturity of fresh leaves, the higher values of phenol ammonia ratio, simple catechins, flavonoid glycosides and peroxidase would be, and one bud with two leaves and one bud with three leaves were significantly higher than single bud and one bud with one leaf (P

Myocardial infarction (MI) is a cardiovascular disease with high morbidity and mortality. Clinically, rehabilitation after massive MI often has a poor prognosis. Therefore, it is necessary to explore the therapeutic methods of myocardial protection after MI. As a first-line treatment for type 2 diabetes, metformin has been found to have a certain protective effect on myocardial tissue. However, its pharmacological mechanism remains unclear. In this study, we investigated key factors that reduced MI with metformin. Through in vivo, in vitro, and in silico analyses, we identified HSF1 as a key target for metformin. HSF1 could up-regulate the transcriptional level of AMPKα2 through transcriptional activation and stimulate the activity of the downstream AMPK/mTOR signaling pathway. Metformin stimulated cardiomyocytes to form stress granules (SGs), and knockdown of HSF1 reversed this process. Furthermore, HSF1 exhibited better in vitro affinity for metformin than AMPK, suggesting that HSF1 may be a more sensitive target for metformin.

In this study, we aimed to identify transplantation tolerance (TOL)-related gene signature and use it to predict the different types of renal allograft rejection performances in kidney transplantation. Gene expression data were obtained from the Gene Expression Omnibus (GEO) database, differently expressed genes (DEGs) were performed, and the gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were also conducted. The machine learning methods were combined to analyze the feature TOL-related genes and verify their predictive performance. Afterward, the gene expression levels and predictive performances of TOL-related genes were conducted in the context of acute rejection (AR), chronic rejection (CR), and graft loss through heatmap plots and the receiver operating characteristic (ROC) curves, and their respective immune infiltration results were also performed. Furthermore, the TOL-related gene signature for graft survival was conducted to discover gene immune cell enrichment. A total of 25 TOL-related DEGs were founded, and the GO and KEGG results indicated that DEGs mainly enriched in B cell-related functions and pathways. 7 TOL-related gene signature was constructed and performed delightedly in TOL groups and different types of allograft rejection. The immune infiltration analysis suggested that gene signature was correlated with different types of immune cells. The Kaplan–Meier (KM) survival analysis demonstrated that BLNK and MZB1 were the prognostic TOL-related genes. Our study proposed a novel gene signature that may influence TOL in kidney transplantation, providing possible guidance for immunosuppressive therapy in kidney transplant patients.

Abstract Liver fibrosis is a progressive histological manifestation that happens in almost all chronic liver diseases. An unabated liver fibrosis may eventually develop into liver cirrhosis or hepatocellular carcinoma. Yet, the strategy for reversal of liver fibrosis is still limited. Herein, a biomimetic nano‐regulator (P‐ZIF8‐cirDNAzyme) is developed to affect both collagen synthesis and degradation in liver to remodel collagen microenvironment. It is found that Zn (II) interference can efficiently inhibit collagen synthesis in activated hepatic stellate cells (aHSC) by inactivating proline 4 hydroxylase and affecting many fibrosis‐related signaling pathways. Meanwhile, Zn (II)‐dependent circular DNAzymes (cirDNAzymes) are used to efficiently silence tissue inhibitors of metalloproteinase‐1, accelerating the degradation of collagen. They act in concert to recover the balance between collagen deposition and degradation. Additionally, ZIF‐8‐cirDNAzyme is coated by platelet membrane (PM) for precisely targeting aHSC via PM's inflammatory tropism and CD62p–CD44 interaction. In carbon tetrachloride‐induced fibrotic mice, P‐ZIF‐8‐cirDNAzyme shows a potent anti‐fibrotic effect, greatly reducing the expression of collagen by 73.12% and restoring liver function nearly to normal. This work proposes a prospective platform enabling ion interference and gene silencing, collectively acting in aHSC for reversal of liver fibrosis.

BackgroundIn recent years, with the continuous development of treatments for hematological malignancies (HMs), the remission and survival rates of patients with HMs have been significantly improved. However, because of severe immunosuppression and long-term recurrent neutropenia during treatment, the incidence and mortality of bloodstream infection (BSI) were all high in patients with HMs. Therefore, we analyzed pathogens’ distribution and drug-resistance patterns and developed a nomogram for predicting 30-day mortality in patients with BSIs among HMs.MethodsIn this retrospective study, 362 patients with positive blood cultures in HMs were included from June 2015 to June 2020 at West China Hospital of Sichuan University. They were randomly divided into the training cohort (n = 253) and the validation cohort (n = 109) by 7:3. A nomogram for predicting 30-day mortality after BSIs in patients with HMs was established based on the results of univariate and multivariate logistic regression. C-index, calibration plots, and decision curve analysis were used to evaluate the nomogram.ResultsAmong 362 patients with BSIs in HMs, the most common HM was acute myeloid leukemia (48.1%), and the most common pathogen of BSI was gram-negative bacteria (70.4%). The final nomogram included the septic shock, relapsed/refractory HM, albumin

BackgroundThe overall survival of peripheral T-cell lymphoma (PTCL) is dismal. Histone deacetylase (HDAC) inhibitors have exhibited promising treatment outcomes for PTCL patients. Therefore, this work aims to systematically evaluate the treatment outcome and safety profile of HDAC inhibitor-based treatment for untreated and relapsed/refractory (R/R) PTCL patients.MethodsThe prospective clinical trials of HDAC inhibitors for the treatment of PTCL were searched on the Web of Science, PubMed, Embase, ClinicalTrials.gov, and Cochrane Library database. The pooled overall response rate, complete response (CR) rate, and partial response rate were measured. The risk of adverse events was evaluated. Moreover, the subgroup analysis was utilized to assess the efficacy among different HDAC inhibitors and efficacy in different PTCL subtypes.ResultsFor untreated PTCL, 502 patients in seven studies were involved, and the pooled CR rate was 44% (95% CI, 39-48%). For R/R PTCL patients, there were 16 studies included, and the CR rate was 14% (95% CI, 11-16%). The HDAC inhibitor-based combination therapy exhibited better efficacy when compared with HDAC inhibitor monotherapy for R/R PTCL patients (P = 0.02). In addition, the pooled CR rate was 17% (95% CI, 13-22%), 10% (95% CI, 5-15%), and 10% (95% CI, 5-15%) in the romidepsin, belinostat, and chidamide monotherapy subgroups, respectively. In the R/R angioimmunoblastic T-cell lymphoma subgroup, the pooled ORR was 44% (95% CI, 35-53%), higher than other subtypes. A total of 18 studies were involved in the safety assessment of treatment-related adverse events. Thrombocytopenia and nausea were the most common hematological and non-hematological adverse events, respectively.ConclusionThis meta-analysis demonstrated that HDAC inhibitors were effective treatment options for untreated and R/R PTCL patients. The combination of HDAC inhibitor and chemotherapy exhibited superior efficacy to HDAC inhibitor monotherapy in the R/R PTCL setting. Additionally, HDAC inhibitor-based therapy had higher efficacy in angioimmunoblastic T-cell lymphoma patients than that in other subtypes.

Abstract Patients with triple‐negative breast cancer (TNBC) have the worst clinical outcomes when compared to other subtypes of breast cancer. Nanotechnology‐assisted photothermal therapy (PTT) opens new opportunities for precise cancer treatment. However, thermoresistance caused by PTT, as well as uncertainty in the physiological metabolism of existing phototherapeutic nanoformulations, severely limit their clinical applications. Herein, based on the clinically chemotherapeutic drug mitoxantrone (MTO), a multifunctional nanoplatform (MTO‐micelles) is developed to realize mutually synergistic mild‐photothermal chemotherapy. MTO with excellent near‐infrared absorption (≈669 nm) can function not only as a chemotherapeutic agent but also as a photothermal transduction agent with elevated photothermal conversion efficacy (ƞ = 54.62%). MTO‐micelles can accumulate at the tumor site through the enhanced permeability and retention effect. Following local near‐infrared irradiation, mild hyperthermia (

Yangchun City, a typical polymetallic ore distribution area in Guangdong Province (China), was selected as the research region to study the content, distribution, source, and possible impacts of heavy metals (HMs) (Arsenic: As; Cadmium: Cd; Chromium: Cr; Copper: Cu; Mercury: Hg; Nickel: Ni; Lead: Pb; and Zinc: Zn) on the farmland soil of this City. According to our findings, the spatial distribution of HMs in Yangchun City shows higher concentrations in the north and southeast and lower in the west and other regions. Metal content in some sampled sites of the agricultural land exceeded the soil pollution risk screening values, particularly As (7.5%), Cd (12%), Cu (4%), Hg (14.5%), and Pb (3%). Additionally, the average content of As, Cu, Cd, Pb, Hg, and Zn from the studied areas surpassed the soil background value of Guangdong Province for all metals. The absolute principal component score-multiple linear regression (APCS-MLR) was used to identify potential sources of HMs in the soil samples. There are three potential sources identified by the model: traffic emissions, natural sources, and agricultural activities, accounting for 28.16%, 16.68%, and 14.42%, respectively. Based on the ecological risk assessment, the potential ecological risk (Eri = 310.77), Nemero pollution index (PN = 2.27), and multiple possible effect concentration quality (mPECQs = 0.23) indicated that the extent of heavy metal pollution in the soil samples was moderate. Three sources were identified: traffic emissions, natural sources, and agricultural activities. We suggest that by combining the above results, a monitoring and early warning system focused on Cd and Hg can be established. The system could utilize geographic information systems and remote sensing technologies to achieve dynamic monitoring and prediction of pollution. Regular testing of soils and sustainable management practices are also recommended to control and remediate contamination.

The co-transport of contaminants by soil colloids can generate substantial environmental risk, and this behavior is greatly affected by environmental conditions. In this study, AF4-ICP-MS was used to investigate the size distribution and composition of Cd/Pb-bearing colloids; saturated sand column experiments were used to investigate the impact of soil colloids on the transport of Cd/Pb under different pH and ionic strength conditions. AF4-ICP-MS characterization showed that natural colloids were primarily associated with two sizes ranges: 0.3–35 KDa (F1, fine nanoparticles) and 280 KDa–450 nm (F2, larger nanoparticles), which mainly consisted of organic matter (OM), iron (Fe), and manganese (Mn) (oxy)hydroxides and clay minerals. Fine nanoparticles could strongly adsorb Cd and Pb under all environmental conditions. Mn and Fe (oxy)hydroxides generally formed under neutral to alkaline conditions and exhibited adsorption capabilities for Cd and Pb, respectively. Transport experiments were conducted under different pH and ionic strength conditions. At pH 3.0, soil colloids had little effect on the transport of Cd2+ and Pb2+. At pH 5.0, soil colloids inhibited the transport of Cd2+ by 16.1%, and Pb2+ recovery was still 0.0%. At pH 7.0 and 9.0, soil colloids facilitated the transport of Cd2+ by 15.6% and 29.6%, facilitated Pb2+ by 1.3% and 6.4%. At an ionic strength of 0, 0.005, and 0.01 mol L−1 NaNO3, soil colloids facilitated the transport of Cd2+ by 77.7%, 45.8%, and 15.6%, only facilitated the transport of Pb2+ by 46.2% at an ionic strength of 0 mol L−1 NaNO3. At an ionic strength of 0.05 mol L−1 NaNO3, soil colloids inhibited the transport of Cd2+ and Pb2+ by 33.1% and 21.0%, respectively. The transport of Cd2+ and Pb2+ facilitated by soil colloids was clearly observed under low ionic strength and non-acidic conditions, which can generate a potential environmental risk.

Argillaceous limestone (AL) is comprised of carbonate minerals and clay minerals and is widely distributed throughout the Earth’s crust. However, owing to its low surface area and poorly active sites, AL has been largely neglected. Herein, manganic manganous oxide (Mn3O4) was used to modify AL by an in-situ deposition strategy through manganese chloride and alkali stepwise treatment to improve the surface area of AL and enable its utilization as an efficient adsorbent for heavy metals removal. The surface area and cation exchange capacity (CEC) were enhanced from 3.49 to 24.5 m2/g and 5.87 to 31.5 cmoL(+)/kg with modification, respectively. The maximum adsorption capacities of lead (Pb2+), copper (Cu2+), and nickel (Ni2+) ions on Mn3O4-modified argillaceous limestone (Mn3O4–AL) in mono-metal systems were 148.73, 41.30, and 60.87 mg/g, respectively. In addition, the adsorption selectivity in multi-metal systems was Pb2+ > Cu2+ > Ni2+ in order. The adsorption process conforms to the pseudo-second-order model. In the multi-metal system, the adsorption reaches equilibrium at about 360 min. The adsorption mechanisms may involve ion exchange, precipitation, electrostatic interaction, and complexation by hydroxyl groups. These results demonstrate that Mn3O4 modification realized argillaceous limestone resourcization as an ideal adsorbent. Mn3O4-modified argillaceous limestone was promising for heavy metal-polluted water and soil treatment.

ABSTRACT: Epidemiologic investigations in recent years have shown that the detection rate of avian hepatitis E virus (HEV) in chicken flocks is increasing in China. Nevertheless, effective prevention and control measures are still lacking. In this study, specific pathogen-free (SPF) chicken serum against HEV was prepared using recombinant HEV open reading frames (ORF2 and ORF3) proteins as immunogens. An SPF chicken infection model was established by intravenous inoculation of chick embryos. Swab samples were collected at 7, 14, 21, and 28 d of age and used to detect avian HEV load, along with other indicators, by fluorescence quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) assay. The therapeutic effects on blocking vertical HEV transmission were observed, by using the methods of antibody application alone, mixed, or combined application of each of the 2 antibodies with type I interferon. The results showed that type I interferon alone or in combination with antiserum reduced the positive rate of HEV from 100 to 62.5% and 25%, respectively. However, the avian HEV-positivity rate was reduced to 75, 50, and 37.5% after type I interferon was used alone or in combination with antisera against ORF2 and ORF3, respectively. The inhibitory effect of type I interferon alone or in combination with an antiserum, on HEV replication was more significant in cells than in vivo. In this study, the inhibitory effect of type I interferon alone or in combination with an antiserum on avian HEV replication was observed in vitro and in vivo, providing the necessary technical reserve for disease prevention and control.

DNA methylation is an important epigenetic modification that regulates many biological processes. The sea cucumber Apostichopus japonicus often suffers from heat stress that affects its growth and leads to significant economic losses. In this study, the mRNA expression patterns and DNA methylation characteristics in the body wall of A. japonicus under heat stress were analyzed by whole-genome bisulfite sequencing (WGBS) and transcriptome sequencing (RNA-seq). We found that CpG was the main DNA methylation type, and heat stress caused a significant increase in the overall methylation level and methylation rate, especially in the intergenic region of the A. japonicus genome. In total, 1,409 differentially expressed genes (DEGs) and 17,927 differentially methylated genes (DMGs) were obtained by RNA-seq and WGBS, respectively. Association analysis between DNA methylation and transcription identified 569 negatively correlated genes in both DMGs and DEGs, which indicated that DNA methylation affects on transcriptional regulation in response to heat stress. These negatively correlated genes were significantly enriched in pathways related to energy metabolism and immunoregulation, such as the thyroid hormone signaling pathway, renin secretion, notch signaling pathway and microRNAs in cancer. In addition, potential key genes, including heat shock protein (hsp70), calcium-activated chloride channel regulator 1(clca1), and tenascin R (tnr), were obtained and their expression and methylation were preliminarily verified. The results provide a new perspective for epigenetic and transcriptomic studies of A. japonicus response to heat stress, and provide a reference for breeding sea cucumbers resistant to high temperatures.