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Abstract In order to solve the problems of long reconstruction time and low reconstruction accuracy of compressed sensing reconstruction algorithm in the measurement of transient signals, a deep unfolding network reconstruction method based on scalable sampling is proposed to achieve fast and high-quality reconstruction of transient signal under low number of measurements. Firstly, the measurement process of compressed sensing is embedded into the neural network to realize automatic design and optimization of the observation matrix, which can reduce the number of measurements. Secondly, scalable sampling is introduced into the measurement process of compressed sensing, which can realize the training of data with different sampling ratios in the same model. Finally, a deep unfolding network model is designed to reconstruct the transient signal, which not only realizes the interpretability of the reconstructed network, but also achieves fast and high-quality reconstruction of the transient signal under the low number of measurements. Experimental results show that compared with the traditional compressed sensing reconstruction algorithms, the proposed method can obtain high-quality reconstruction accuracy with lower measurement times, and the reconstruction time is greatly reduced. The algorithm in this paper also obtains good reconstruction results under different sampling ratios, which shows that the method in this paper has good adaptability and effectiveness.

Abstract T helper cells, particularly T follicular helper (TFH) cells, are essential for the neutralizing antibody production elicited by pathogens or vaccines. However, in immunocompromised individuals, the inefficient support from TFH cells could lead to limited protection after vaccine inoculation. Here we showed that the conjugation of inducible T cell costimulatory (ICOS) onto the nanoparticle, together with immunogen, significantly enhanced the immune response of the vaccines specific for SARS-CoV-2 or human immunodeficiency virus type-1 (HIV-1) in TFH-deficient mice. Further studies indicated that ICOSL on B cells was triggered by ICOS binding, subsequently activated the PKCβ signaling pathway, and enhanced the survival and proliferation of B cells. Our findings revealed that the stimulation of ICOS-ICOSL interaction by adding ICOS on the nanoparticle vaccine significantly substitutes the function of TFH cells to support B cell response, which is significant for the immunocompromised people, such as the elderly or HIV-1-infected individuals.

This paper contributes to the classification of flag-transitive 2-$ (v, k, \lambda) $ designs. Let $ \mathcal{D} $ be a non-trivial and non-symmetric $ 2 $-$ (v, k, \lambda) $ design with $ \lambda $ prime and $ G $ be a flag-transitive point-primitive automorphism group of $ \mathcal{D} $. A recent work by the first author and Chen has proven that the socle of $G$ is either a nonabelian simple group or an elementary abelian $ p $-group for some prime $ p $. In this paper, we focus on the case where the socle of $G$ is an exceptional group of Lie type and give all possible parameters of such 2-designs.

Objective To explore the epidemiological characteristics of voluntary blood donors with enzyme-linked immuno-sorbent assay (ELISA) negative and nucleic acid testing (NAT) positive in Hainan from 2012 to 2022, so as to provide reference for developing rational blood screening strategies. Methods The screening results for transfusion-transmitted disease markers in 1 161 042 blood samples in Hainan from 2012 to 2022 were retrospectively analyzed. All samples have been measured twice by ELISA and once by NAT. Statistical methods were used to analyze the proportion of ELISA negative and NAT positive (ELISA-/NAT+ ) among voluntary blood donors and its relation with factors including gender, age, ethnicity and region. Results Among the voluntary blood donors in Hainan from 2012 to 2022, the overall proportion of ELISA-/NAT+ was 0.19% (2 151/1 161 042), and the difference was statistically significant (P

Abstract Fast computational ghost imaging with high quality and ultra-high-definition resolution reconstructed images has important application potential in target tracking, biological imaging and other fields. However, as far as we know, the resolution (pixels) of the reconstructed image is related to the number of measurements. And the limited resolution of reconstructed images at low measurement times hinders the application of computational ghost imaging. Therefore, in this work, a new computational ghost imaging method based on saliency variable sampling detection is proposed to achieve high-quality imaging at low measurement times. This method physically variable samples the salient features and realizes compressed detection of computational ghost imaging based on the salient periodic features of the bucket detection signal. Numerical simulation and experimental results show that the reconstructed image quality of our method is similar to the compressed sensing method at low measurement times. Even at 500 (sampling rate $$0.76\%$$ 0.76 % ) measurement times, the reconstructed image of the method still has the target features. Moreover, the $$2160\times 4096$$ 2160 × 4096 (4K) pixels ultra-high-definition resolution reconstructed images can be obtained at only a sampling rate of $$0.11\%$$ 0.11 % . This method has great potential value in real-time detection and tracking, biological imaging and other fields.

Abstract Tomosyns are widely thought to attenuate membrane fusion by competing with synaptobrevin-2/VAMP2 for SNARE-complex assembly. Here, we present evidence against this scenario. In a novel mouse model, tomosyn-1/2 deficiency lowered the fusion barrier and enhanced the probability that synaptic vesicles fuse, resulting in stronger synapses with faster depression and slower recovery. While wild-type tomosyn-1m rescued these phenotypes, substitution of its SNARE motif with that of synaptobrevin-2/VAMP2 did not. Single-molecule force measurements indeed revealed that tomosyn’s SNARE motif cannot substitute synaptobrevin-2/VAMP2 to form template complexes with Munc18-1 and syntaxin-1, an essential intermediate for SNARE assembly. Instead, tomosyns extensively bind synaptobrevin-2/VAMP2-containing template complexes and prevent SNAP-25 association. Structure-function analyses indicate that the C-terminal polybasic region contributes to tomosyn’s inhibitory function. These results reveal that tomosyns regulate synaptic transmission by cooperating with synaptobrevin-2/VAMP2 to prevent SNAP-25 binding during SNARE assembly, thereby limiting initial synaptic strength and equalizing it during repetitive stimulation.

Abstract Background Chimeric antigen receptor-T (CAR-T) cells therapy is one of the novel immunotherapeutic approaches with significant clinical success. However, their applications are limited because of long preparation time, high cost, and interpersonal variations. Although the manufacture of universal CAR-T (U-CAR-T) cells have significantly improved, they are still not a stable and unified cell bank. Methods Here, we tried to further improve the convenience and flexibility of U-CAR-T cells by constructing novel modular universal CAR-T (MU-CAR-T) cells. For this purpose, we initially screened healthy donors and cultured their T cells to obtain a higher proportion of stem cell-like memory T (TSCM) cells, which exhibit robust self-renewal capacity, sustainability and cytotoxicity. To reduce the alloreactivity, the T cells were further edited by double knockout of the T cell receptor (TCR) and class I human leukocyte antigen (HLA-I) genes utilizing the CRISPR/Cas9 system. The well-growing and genetically stable universal cells carrying the CAR-moiety were then stored as a stable and unified cell bank. Subsequently, the SDcatcher/GVoptiTag system, which generate an isopeptide bond, was used to covalently connect the purified scFvs of antibody targeting different antigens to the recovered CAR-T cells. Results The resulting CAR-T cells can perform different functions by specifically targeting various cells, such as the eradication of human immunodeficiency virus type 1 (HIV-1)-latenly-infected cells or elimination of T lymphoma cells, with similar efficiency as the traditional CAR-T cells did. Conclusion Taken together, our strategy allows the production of CAR-T cells more modularization, and makes the quality control and pharmaceutic manufacture of CAR-T cells more feasible.

IntroductionFengxiangxing Huairang Daqu (FHD) is one of the major types of Daqu in China. However, the relationship between the microbial community structure at different stages, the changes in the sensory characteristics, fermentation characteristics, volatiles, the most critical process point, and the quality formation of FHD is not clear.MethodsBased on microscopic characterization, PacBio SMRT sequencing, and HS-SPME-GC-MS volatile metabolite analysis revealed the relationship between FHD quality formation and the dynamics of Qupi.ResultsThe results showed that the 12th day of the culture was the most critical process point, highlighting the most significant differences in microbial community structure, sensory characteristics, fermentation characteristics, and flavor substances. Bacillus licheniformis (43.25%), Saccharopolyspora rectivirgula (35.05%), Thermoascus aurantiacus (76.51%), Aspergillus amstelodami (10.81%), and Saccharomycopsis fibuligera (8.88%) were the dominant species in FHD. S. fibuligera, A. amstelodami, and T. aurantiacus were associated with the snow-white color of the FHD epidermis, the yellow color of the interior, and the gray-white color, respectively. The abundance of T. aurantiacus, A. amstelodami, B. licheniformis, and S. rectivirgula was positively associated with the esterifying power and liquefying power of FHD. The abundance of T. aurantiacus and A. amstelodami was positively correlated with the saccharifying power of FHD. The abundance of S. fibuligera was positively related to the fermenting power of FHD. A total of 248 volatiles were detected in Qupi, mainly including alcohols, esters, aldehydes, and ketones. Of them, eleven volatiles had a significant effect on the flavor of Qupi, such as 1-butanol-3-methyl-, hydrazinecarboxamide, ethanol, phenylethyl alcohol, ethyl acetate, 2-octanone, 1-octen-3-ol, formic acid-hexyl ester, (E)-2-octen-1-ol, ethyl hexanoate, and 2(3H)-furanone-dihydro-5-pentyl-. The abundance of B. licheniformis, S. rectivirgula, T. aurantiacus, and S. fibuligera was positively correlated with the alcohols, aromatic compounds, and phenols in FHD. The abundance of S. fibuligera was positively correlated with the acids, esters, and hydrocarbons in FHD.DiscussionThese results indicate important theoretical basis and technical support for controllable adjustment of FHD microbial community structure, stable control of FHD quality, and precise, effective, and large-scale guidance of FHD production.

From the late Carboniferous to the early Permian, multiple pulses of glaciation and deglaciation have been caused by the LPIA. The Pennsylvanian period experienced phases of recovery, proliferation, and decline, ultimately forming a reef system distinctly different from that of the Mississippian period. During the late Bashkirian to Moscovian, the metazoan reef experienced a limited resurgence, with reef predominantly formed by chaetetid developing in the United States, northern China, and Japan. During the Kasimovian to Gzhelian, the phylloid algal reef dominated the global reef systems. In the late Pennsylvanian, bioconstruction cases and paleoenvironmental proxies in southern Guizhou Province were studied to investigate the composition, recovery, and evolutionary processes of the bioconstructions as well as their response to environmental variations during this period. Several bioconstructions have been reported in the Lumazhai section of Houchang Town, Guizhou Province, southern China, from the Moscovian to the Gzhelian. The upper Carboniferous strata are well-preserved and continuously exposed. The continuous strata, abundant fossils, and diverse bioconstructions provide excellent research materials for exploring the mutual constraints between organisms and their environment. This study identified ten microfacies, whose vertical evolution indicated significant changes in the depositional environment related to relative sea-level fluctuations. Skeletal grains are widely present in these facies. Among them, foraminifera, algae, bryozoans, crinoids, and Tubiphytes are the most common and exhibit distinct distribution characteristics in various environments. Quantitative statistics, CCA and theoretical ecospace have been utilized to examine and interpret environmental impact factors. Quantitative analysis of their relative abundance and distribution patterns provides insights into the complex interactions between organisms and environmental factors. The relative abundances of different organisms and factors controlling their bioconstructions are influenced by relative sea-level changes. CCA analysis reveal that hydrodynamic conditions are the primary influencing factor. Variation trends in average tiering and motility reveal the characteristics of biological communities during environmental changes in phylloid algae and microbial bioconstructions. These bioconstructions are not directly correlated with changes in environmental factors, and the biological communities in phylloid algae mounds and biostromes exhibit similar organism compositions and ecological niches across different environments.

Prolonged exposure to ultraviolet (UV) irradiation can cause oxidative stress in the skin, accompanied by rapid immunosuppressive effects, resulting in a peroxidation reaction throughout the body. Curcumin (Cur), as the bioactive compound of turmeric, is a natural polyphenol with potent antioxidant properties but is often overlooked due to its poor solubility and low bioavailability. In this study, curcumin-loaded liposomes in a sodium alginate gel complex preparation were designed to improve the bioavailability of curcumin and to study its preventive effect on photodamage. Cur-loaded liposomes (Cur-L), Cur-loaded gel (Cur-G) based on an alginate matrix, and curcumin-loaded liposomes in gel (Cur-LG) were prepared, and their antioxidant effects and drug diffusion abilities were evaluated. The antioxidant capacity of Cur, Cur-L, Cur-G, and Cur-LG was also studied in a mouse model of photodamage. Cur had the highest antioxidant activity at about 4 mg/mL. Cur-LG at this concentration showed antioxidant effects during 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH) and H2O2 experiments. During the UV light damage test, Cur-LG demonstrated the ability to effectively neutralize free radicals generated as a result of lipid peroxidation in the skin, serum, and liver, thereby enhancing the overall activity of superoxide dismutase (SOD). In conclusion, using Cur-LG may protect against epidermal and cellular abnormalities induced by UV irradiation.

Abstract Background Auriculocondylar syndrome (ARCND) is a rare congenital craniofacial developmental malformation syndrome of the first and second pharyngeal arches with external ear malformation at the junction between the lobe and helix, micromaxillary malformation, and mandibular condylar hypoplasia. Four subtypes of ARCND have been described so far, that is, ARCND1 (OMIM # 602483), ARCND2 (ARCND2A, OMIM # 614669; ARCND2B, OMIM # 620458), ARCND3 (OMIM # 615706), and ARCND4 (OMIM # 620457). Methods This study reports a case of ARCND2 resulting from a novel pathogenic variant in the PLCB4 gene, and summarizes PLCB4 gene mutation sites and phenotypes of ARCND2. Results The proband, a 5‐day‐old male neonate, was referred to our hospital for respiratory distress. Micrognathia, microstomia, distinctive question mark ears, as well as mandibular condyle hypoplasia were identified. Trio‐based whole‐exome sequencing identified a novel missense variant of NM_001377142.1:c.1928C>T (NP_001364071.1:p.Ser643Phe) in the PLCB4 gene, which was predicted to impair the local structural stability with a result that the protein function might be affected. From a review of the literature, only 36 patients with PLCB4 gene mutations were retrieved. Conclusion As with other studies examining familial cases of ARCND2, incomplete penetrance and variable expressivity were observed within different families' heterozygous mutations in PLCB4 gene. Although, motor and intellectual development are in the normal range in the vast majority of patients with ARCND2, long‐term follow‐up and assessment are still required.

The effect of ivermectin (IVM) in treating coronavirus disease 2019 (COVID-19) is still controversial, yet the drug has been widely used in the world. The aim of this review was to systematically evaluate the clinical outcomes of IVM in patients with COVID-19. From inception to June 22, 2023, the PubMed, EMBASE, Web of Science (WOS), and scopus databases were searched for relevant observational studies on the risk of RA in migraineurs. We searched PubMed/Medline, EMBASE, the Cochrane Library, Web of Science, medRxiv, and bioRxiv to collect all relevant publications from inception to June 22, 2023. Primary outcomes were all-cause mortality rate, mechanical ventilation (MV) requirement, PCR negative conversion, and adverse events (AEs). Revman 5.4 was used to assess the risk of bias (RoB) and quality of evidence. Thirty-three RCTs (n = 10,489) were included. No significant difference in all-cause mortality rates or PCR negative conversion between IVM and controls. There were significant differences in MV requirement (RR 0.67, 95% CI 0.47–0.96) and AEs (RR 0.87, 95% CI 0.80–0.95) between the two groups. Ivermectin could reduce the risk of MV requirement and AEs in patients with COVID-19, without increasing other risks. In the absence of a better alternative, clinicians could use it with caution.

Abstract To reduce the gas disaster of high gas coal seam and improve the efficiency of gas extraction by high drilling, the layout parameters of drilling holes in Pingdingshan coal mine are optimized. Based on the analysis and calculation of the "three zones" of the movement towards the overly strata of No.10 coal in Pingdingshan coal mine, the height of caving zone and fissure zone in 24,130 working face are 10.06–14.46 m and 38.75–49.95 m respectively. The elevation angle, azimuth angle and the length of high-level boreholes are studied and analyzed by COMSOL numerical simulation software. The simulation results show that the optimum layout parameters of high-level boreholes are as follows: The elevation angle of borehole should be controlled at 9°–12°, the azimuth angle should be 30°–45°, and the length of borehole should be 150 m. Then the optimum layout parameters of high-level boreholes are determined for engineering application of 24,130 working face. Borehole data onto actual mine show that the optimum layout parameters of high-level boreholes were elevation angle between 8°and 11°, azimuth angle between 30° and 42°, and length of boreholes between 145 and 155 m. The simulation results are basically consistent with the measured data. The maximum gas concentration in working face, upper corner and return air roadway is stably controlled below 1%. The safe mining of 24,130 working face is ensured, which provided a certain reference value of gas control in the goaf of Pingdingshan mine and adjacent mines.

A dynamic southern branch trough （SBT） and a dynamic northern branch ridge （NBR）， two flows around the Tibetan Plateau （FQXP） generated by the mid-latitude westerlies in the winter half-year （October-April）， have an important influence on the weather and climate of their vicinity and downstream.In this paper， differences between the mean vorticity and the multi-year mean vorticity of two key regions-where the SBT and the NBR are located in 600 hPa are used to represent the intensity of the SBT and the NBR separately.Then the difference between the strength of SBT and NBR is defined visually as the intensity index of FQXP.The relationship between the precipitation and temperature in China and the evolution of FQXP's average in winter half-year and that in autumn， winter and spring is discussed， using correlation analysis and composite analysis.The results show that the FQXP is constant in the winter half-year （October-April）， with significant interannual variations， and the strongest in winter.In the context of global warming， variations in the intensity of FQXP at each period is closely related to the precipitation and temperature in Northwest， Southwest and South China， especially in winter.FQXP has a significant relationship with the temperature changes in northwest， southwest and northeast China， and its best precipitation correlations are found in southwest and south China.Analysis of anomalous large-scale atmospheric circulation and physical quantity fields， such as water vapor flux dispersion and vertical velocity， at each layer in each time period leads to the conclusion that the bottom-up positive pressure characteristic is significant in most of Asia， which well explains the relationship between FQXP anomalies and precipitation and temperature in China at each time period.FQXP anomalies may also be one cause for high-impact weather in China during winter half-year.

Abstract Background Craniofacial microsomia (CFM) is a common congenital malformation with unknown pathogenesis. Although few cases have been reported, it is suggested that variants of the SF3B2 gene may lead to CFM. We herein report the case of a neonate with CFM exhibiting rare features of airway obstruction. Methods Trio whole‐exome sequencing and Sanger validation were performed on the proband and her parents. Candidate gene mutations were analyzed using the Genome Aggregation Database (gnomAD) for normal frequency distributions. The Human Splicing Finder (HSF) and Rare Disease Data Center (RDDC) RNA splicer algorithms predicted the variant's harmfulness, verified by a Minigene assay. Results The proband had a heterozygous SF3B2 variant, NM_006842.3:c.777+1G>A. The patient's father also carried this variant and exhibited facial abnormalities. The variant was not in gnomAD, and HSF and RDDC RNA splicers indicated donor site disruption. The minigene assay suggested that two mRNA products were produced, leading to a premature termination codon. Conclusion For this family, the pathogenesis of CFM may have been caused by an SF3B2 splicing variant. Affected family members exhibited varying degrees of malformation, indicating that CFM has phenotypic heterogeneity. This finding expands the phenotype and variant spectrum of SF3B2, enriches neonatal CFM research, and provides a possible guide to genetic counseling.

There are two kinds of chlorites occurred in Anshan area, among which the hydrothermal Fe-chlorite with longer Fe-OH wavelength is spatially related to the high-grade magnetite ore, meaning that wavelength mapping of chlorites can be used to target the BIF-hosted high grade iron ore. In this article, quadratic polynomial, cubic spline, and quartic polynomial method were used to interpolate the absorption wavelength near 2250 nm of China ZY1-02D satellite hyperspectral image. The result of quadratic polynomial is continuous without data overlapping or intervals, thus most suitable for discrimination of the chlorites. The field truth shows that the spatial distribution of Fe-chlorite, validated by XRD analysis, is not only in accordance with that of high grade magnetite ore bodies, but also consistent with the recently discovered concealed iron bonanza. The study shows that hyperspectral remote sensing techniques can play significant role in the exploration of magnetite iron ore in east Liaoning Province.

WRKY transcription factors (TFs) have been identified as important core regulators in the responses of plants to biotic and abiotic stresses. Cultivated peanut (Arachis hypogaea) is an important oil and protein crop. Previous studies have identified hundreds of WRKY TFs in peanut. However, their functions and regulatory networks remain unclear. Simultaneously, the AdWRKY40 TF is involved in drought tolerance in Arachis duranensis and has an orthologous relationship with the AhTWRKY24 TF, which has a homoeologous relationship with AhTWRKY106 TF in A. hypogaea cv. Tifrunner. To reveal how the homoeologous AhTWRKY24 and AhTWRKY106 TFs regulate the downstream genes, DNA affinity purification sequencing (DAP-seq) was performed to detect the binding sites of TFs at the genome-wide level. A total of 3486 downstream genes were identified that were collectively regulated by the AhTWRKY24 and AhTWRKY106 TFs. The results revealed that W-box elements were the binding sites for regulation of the downstream genes by AhTWRKY24 and AhTWRKY106 TFs. A gene ontology enrichment analysis indicated that these downstream genes were enriched in protein modification and reproduction in the biological process. In addition, RNA-seq data showed that the AhTWRKY24 and AhTWRKY106 TFs regulate differentially expressed genes involved in the response to drought stress. The AhTWRKY24 and AhTWRKY106 TFs can specifically regulate downstream genes, and they nearly equal the numbers of downstream genes from the two A. hypogaea cv. Tifrunner subgenomes. These results provide a theoretical basis to study the functions and regulatory networks of AhTWRKY24 and AhTWRKY106 TFs.

Abstract Analysis of the changes of microorganisms during Chinese Feng-flavor Daqu fermentation, and the specific contribution of different environmental factors to Daqu microorganisms. High throughput sequencing technology and SourceTracker software were used to analyze the microbial diversity of Feng-flavor Daqu before and after fermentation. 85 fungal and 105 bacterial were detected in the newly pressed Feng-flavor Daqu, while 33 fungal and 50 bacterial in the mature Daqu, and 202 fungal and 555 bacterial in the environmental samples. After fermentation, the microbial community structure of Daqu changed and decreased significantly. 94.7% of fungi come from raw materials and 1.8% from outdoor ground, 60.95% of bacteria come from indoor ground, 20.44% from raw materials, and 8.98% from tools. By comparing the changes of microorganisms in Daqu before and after fermentation, the microorganisms in mature Daqu may mainly come from not only the enhanced strains but also the environment.The source of main microorganisms in Feng-flavor Daqu and the influence of environmental factors on the quality of Daqu were clarified, which provided a basis for improving the quality of Feng-flavor Daqu.

The spatial complexity of oil shale systems is manifested by microstructure, pore space randomness and extensive heterogeneity. A microwave pyrolysis device developed for this study was used to pyrolyze oil shale, and the microstructure before and after pyrolysis was visually examined and quantified. The internal structure of the rock and the extent of pore and fracture expansion are more accurately determined in this way. The microstructure of oil shale at different temperatures before and after microwave pyrolysis is identified by X-ray microcomputed tomography (μCT) with automatic ultra-high-resolution scanning electron microscopy (SEM), to observe the heterogeneous state of oil shale on 2D and 3D scales and define the distribution of internal pores and fractures by post-processing μCT visualization. The study found that fractures sized from microns to millimeters along with pore fractures were observed at increasing microwave temperatures. The fractures gradually expanded with increasing temperature in the direction of horizontal or vertical laminae and generated a more connected pore network. The kerogen gradually decreased with a rise in temperature. The porosity increased from 0.26% to 13.69% at the initial temperature. This research is essential for the qualitative as well as quantitative analysis of the internal structure of oil shales under microwave radiation.

Abstract Background Ovarian cancer is one of the most lethal cancers in women because it is often diagnosed at an advanced stage. The molecular markers investigated thus far have been unsatisfactory. Methods We performed whole-exome sequencing on the human ovarian cancer cell lines 3AO and ES2 and the normal ovarian epithelial cell line IOSE-80. Molecular markers of ovarian cancer were screened from shared mutation genes and copy number variation genes in the 6q21-qter region. Results We found that missense mutations were the most common mutations in the gene (93%). The MUC12, FLG and MUC16 genes were highly mutated in 3AO and ES2 cells. Copy number amplification occurred mainly in 4p16.1 and 11q14.3, and copy number deletions occurred in 4q34.3 and 18p11.21. A total of 23 hub genes were screened, of which 16 were closely related to the survival of ovarian cancer patients. The three genes CCDC170, THBS2 and COL14A1 are most significantly correlated with the survival and prognosis of ovarian cancer. In particular, the overall survival of ovarian cancer patients with high CCDC170 gene expression was significantly prolonged (P

Orthopoxviruses (OPXVs) belong to a group of nucleo-cytoplasmic large DNA viruses. Human pathogenic OPXVs (hpOPXVs) include at least five viruses, among which smallpox virus and monkeypox virus are the most dangerous viral pathogens. Both viruses are classified as category-one human infectious pathogens in China. Although smallpox was globally eradicated in the 1980 s, it is still a top biosecurity threat owing to the possibility of either being leaked to the outside world from a laboratory or being weaponized by terrorists. Beginning in early May 2022, a sudden outbreak of monkeypox was concurrently reported in more than 100 disparate geographical areas, representing a public health emergency of international concern, as declared by the World Health Organization (WHO). In this review, we present the reasons for hpOPXVs such as monkeypox virus presenting a potential threat to public health. We then systematically review the historical and recent development of vaccines and drugs against smallpox and monkeypox. In the final section, we highlight the importance of viromics studies as an integral part of a forward defense strategy to eliminate the potential threat to public health from emerging or re-emerging hpOPXVs and their variants.

Abstract Because of the rapid mutation and high airborne transmission of SARS‐CoV‐2, a universal vaccine preventing the infection in the upper respiratory tract is particularly urgent. Here, a mosaic receptor‐binding domain (RBD) nanoparticle (NP) vaccine is developed, which induces more RBD‐targeted type IV neutralizing antibodies (NAbs) and exhibits broad cross‐protective activity against multiple SARS‐CoV‐2 sublineages including the newly‐emerged BF.7, BQ.1, XBB. As several T‐cell‐reactive epitopes, which are highly conserved in sarbecoviruses, are displayed on the NP surface, it also provokes potent and cross‐reactive cellular immune responses in the respiratory tissue. Through intranasal delivery, it elicits robust mucosal immune responses and full protection without any adjuvants. Therefore, this intranasal mosaic NP vaccine can be further developed as a pan‐sarbecovirus vaccine to block the viral entrance from the upper respiratory tract.

Facial palsy would lead to a series of physical and mental problems, as facial function plays an important role in various aspects of daily life. However, the current strategies for evaluating facial function relied heavily on raters and the results varied from the experience of raters. Thus, an objective and accurate facial evaluation system is always claimed. In this study, a customized automatical facial evaluation system (AFES) was proposed, which might have the potential to be employed as an adjunctive and efficient assessing method in clinic. In order to investigate the feasibility of AFES, ninety-two participants with facial palsy were recruited and received scale-based subjective manual evaluation (including mHBGS and mSFGS) and objective automatical evaluation of AFES (including aHBGS, aSFGS and indicators of facial regional features) at enrollment and after two weeks. The correlations between the results of the two methods were analyzed and the participants were stratified according to the severity of facial function for further analyses. Strong positive correlations between manual and automatical HBGS and SFGS were observed and higher correlations were reported in the participants with normal-mild and moderate facial palsy. Significant improvements in clinical scales and indicator of eye synkinesis were found in forty-two participants in two weeks. Furthermore, some of the indicators were correlated with scale scores (I4, I7) and one of them presented a significant change between the baseline evaluation and follow-up evaluation (I7). According to the results, AFES could be considered as a viable method to perform objective and reliable evaluation for patients with facial palsy and provide clarified results for prognosis.

Abstract Background With d-xylose being the second most abundant sugar in nature, its conversion into products could significantly improve biomass-based process economy. There are two well-studied phosphorylative pathways for d-xylose metabolism. One is isomerase pathway mainly found in bacteria, and the other one is oxo-reductive pathway that always exists in fungi. Except for these two pathways, there are also non-phosphorylative pathways named xylose oxidative pathways and they have several advantages over traditional phosphorylative pathways. In Myceliophthora thermophila, d-xylose can be metabolized through oxo-reductive pathway after plant biomass degradation. The survey of non-phosphorylative pathways in this filamentous fungus will offer a potential way for carbon-efficient production of fuels and chemicals using d-xylose. Results In this study, an alternative for utilization of d-xylose, the non-phosphorylative Weimberg pathway was established in M. thermophila. Growth on d-xylose of strains whose d-xylose reductase gene was disrupted, was restored after overexpression of the entire Weimberg pathway. During the construction, a native d-xylose dehydrogenase with highest activity in M. thermophila was discovered. Here, M. thermophila was also engineered to produce 1,2,4‐butanetriol using d-xylose through non-phosphorylative pathway. Afterwards, transcriptome analysis revealed that the d-xylose dehydrogenase gene was obviously upregulated after deletion of d-xylose reductase gene when cultured in a d-xylose medium. Besides, genes involved in growth were enriched in strains containing the Weimberg pathway. Conclusions The Weimberg pathway was established in M. thermophila to support its growth with d-xylose being the sole carbon source. Besides, M. thermophila was engineered to produce 1,2,4‐butanetriol using d-xylose through non-phosphorylative pathway. To our knowledge, this is the first report of non-phosphorylative pathway recombinant in filamentous fungi, which shows great potential to convert d-xylose to valuable chemicals.

On a microwave radiation triaxial loading experimental system with independent intellectual property rights, seepage experiments of coal samples were condected under the action of different microwave radiation power, radiation time, and effective force, the key factors affecting the permeability of coal samples were analysed, and the actual structural coal seam infiltration was reasonably predicted. According to the heating experiments, the fitted formula of surface temperature, radiant powers and radiation time of coal samples was obtained. The main influencing factors of permeability: effective force, radiated power, and their sensitivity were analyzed. The synergistic permeation of radiation power and radiation time in the form of energy consumption ratio was draum. It is concluded that higher microwave power infiltration should be selected. Through the analysis of the influence of radiation power, radiation time, and effective force on coal sample permeability, the mechanism of microwave radiation permeation increase is clearar, which has a theoretical reference and guidance for the capacity prediction of microwave radiant thermal recovery technology.

Abstract The aphasia quotient of Western Aphasia Battery (WAB-AQ) has been used as an inclusion criterion and as an outcome measure in clinical, research, or community settings. The WAB-AQ is also commonly used to measure recovery. This study aimed to quantitatively determine levels of the linguistic deficit by using a cluster analysis of the WAB-AQ in post-stroke aphasia (PSA). 308 patients were extracted from the database. Cutoff scores are defined by mean overlap WAB-AQ scores of clusters by systematic cluster analysis, the method of which is the farthest neighbor element, and the metrics are square Euclidean distance and Pearson correlation, performed on the full sample of WAB-AQ individual subitem scores. A 1-way analysis of variance, with post hoc comparisons conducted, was used to determine whether clusters had significant differences. Three clusters were identified. The scores for severe, moderate, and mild linguistic deficit levels ranged from 0 to 30, 30.1 to 50.3, and 50.4 to 93.7, respectively. For PSA, the cluster analysis of WAB-AQ supports a 3-impairment level classification scheme.

Methyl gallate (MG) is a polyphenolic compound widely found in natural plants. MG has been shown to have a variety of biological functions, including anti-tumor, anti-inflammatory, anti-oxidant, neuroprotective, hepatoprotective and anti-microbial activities, and has broad research and development prospects. A total of 88 articles related to MG were searched using the PubMed, Science Direct, and Google Scholar databases, systematically investigating the pharmacological activity and molecular mechanisms of MG. There were no restrictions on the publication years, and the last search was conducted on June 5, 2023. MG can exert pharmacological effects through multiple pathways and targets, such as PI3K/Akt, ERK1/2, Caspase, AMPK/NF-κB, Wnt/β-catenin, TLR4/NF-κB, MAPK, p53, NLRP3, ROS, EMT. According to the literature, MG has the potential to be a prospective adjuvant for anticancer therapy and deserves further study.

With the rapid development of international energy trade, its structure has shown a trend toward complexity and network development. The traditional unilateral or bilateral perspective of causal analysis can no longer explain the changes in the international energy trade network at this stage. This paper constructs the world energy trade network from 2000 to 2020, analyzes the structural characteristics of the network, and adopts the quadratic assignment procedure method to deconstruct and explain the structural evolution of the world energy trade network. The study shows that the global energy trade network is increasingly connected and has small-world characteristics; the growing global energy demand coexists with the increasing energy monopoly; GDP difference and geographical distance are the decisive factors in forming an international energy trade network. It is suggested that countries should strengthen the integrated development of energy trade; formulate differentiated regional policies according to the structure and economic development characteristics of national and regional energy trade; pay more attention to the hub vertexes in the international energy trade network; and formulate differentiated energy strategies for countries and regions with different development levels, taking into account their development situations.

Chip is the “brain” of the information industry and modern manufacturing industry, and supply chain security is the key to the sustainable development of the industrial chain. From the perspective of the industrial chain, this paper selected semiconductor silicon wafers and equipment, integrated circuits, electronic computers, and components as representative commodities in the upstream, midstream, and downstream of the chip industry chain, constructed global trade networks of the chip industry chain, and analyzed the characteristics of the networks and nodes in 2020 and the changes in China's status before and after the China-U.S. tech war. The study results indicate that the network scale and network density of the global trade network of downstream electronic computers and components are higher than those of midstream integrated circuits; the global trade network of upstream semiconductor wafers and equipment has the smallest network scale and network density, and the trade networks of all links show obvious small-world characteristics; The United States ranks first in betweenness centrality of all links, with the strongest control ability and the largest number of trading partners in all links; China has higher betweenness centrality and more trading partners in the global trade network of the two upstream commodities than that of the midstream commodities, and the lowest betweenness centrality in the global trade network of the downstream commodities; The core countries of the chip industry chain are concentrated in southeast Asia, east Asia, central and western Europe, and the United States. China's trade status of semiconductor silicon wafers and integrated circuits has declined significantly during the China-U.S. tech war. The nodes in the chip trade network have good robustness in the face of random attacks and show vulnerability under target attacks. Additionally, the trade network's robustness in the chip industry chain is the strongest for downstream commodities, ranks second for midstream commodities, and is the weakest for upstream commodities. These findings can provide references for ensuring chip supply chain security in China and other trade-participating countries.

This paper contributes to the classification of flag-transitive symmetric 2-(v,k,λ) designs with λ prime. We investigate the structure of flag-transitive, point-quasiprimitive automorphism groups (G) of such 2-designs by applying the classification of quasiprimitive permutation groups. It is shown that the automorphism groups (G) have either an abelian socle or a non-abelian simple socle. Moreover, according to the classification of finite simple groups, we demonstrate that point-quasiprimitivity implies point-primitivity of G, except when the socle of G is PSLn(q).

Abstract The present study aimed to investigate the functional properties of soybean protein isolate (SPI) treated with alkaline protease and high-speed shearing homogenization. Alkaline protease-hydrolyzed SPIs that were characterized by varying degrees of hydrolysis between 0 and 6% were treated with high-speed shearing homogenization to obtain different micro-particulate proteins. The results showed that this combined treatment could significantly reduce the particle size of SPI by markedly degrading the structure of both the 7S and 11S subunits, thereby resulting in a significantly reduced content of β-sheet and β-turn structures. The surface hydrophobicity increased considerably for samples with hydrolysis below the threshold of 2% and then declined gradually above this threshold. Furthermore, the combination of hydrolysis and homogenization significantly improved the emulsion stability of SPI hydrolysates. It also significantly improved the foaming properties of SPI. These results demonstrated that alkaline protease hydrolysis combined with high-speed shearing homogenization represents a promising approach for improving the functional and structural properties of SPI. Graphical Abstract

The spatial distribution and seasonal variation of near-inertial kinetic energy (NIKE) in the upper Ross Sea (RS) are examined using the 1/4° NEMO3.6-LIM3 sea ice physical–biological coupled model. The annual-mean surface and mixed layer-integrated NIKE have large values at the shelf break around Iselin Bank and the northeast area outside the continental shelf. The spatial distribution of the surface and mixed layer-integrated NIKE in the austral summer RS is mainly controlled by the near-inertial wind stress magnitude (NIWSM), which acts as the energy source. The northeast high NIKE agrees with the large NIWSM there. Semidiurnal tides only contribute to the NIKE peak around the Iselin Bank and shelf break. The change of mixed layer depth (MLD) can induce spatial discrepancies between surface and mixed layer-integrated NIKE. The shallower MLD in the western RS limits the near-inertial energy in a thin layer, which has induced the large surface NIKE there. The NIKE in the upper RS has a pronounced seasonal variation with the largest surface and mixed layer-integrated NIKE both observed during austral summer. The seasonal variation of NIWSM and sea ice concentration play an important role in inducing the seasonal variation of NIKE. While the NIWSM acts as the main energy source of NIKE, the presence of sea ice can prevent the wind from directly acting on the surface ocean, inducing the low NIKE during austral winter.

The stock risk spillovers of 31 associated enterprises of Evergrande supply chain in China were measured with DCC-GARCH and CoVaR model, and high, moderate and low risk overflow networks in four periods were constructed, finally the overall metrics and dynamic evolution of risk spillover network were explored. The results showed that: With COVID-19 under control in China, the risk spillover of Evergrande supply chain associated enterprises continues to diverge, with the quantity and scope of high risk declining and moderate and low risk rising; The infection scope of high risk spillover has narrowed, from indirect to direct infection; Evergrande subsidiaries play obvious bridge roles in moderate and low risk networks, have strong control over the risk spread; Commercial banks suffer and trigger more risk spillovers, a number of risk spillover groups with commercial banks as cores formed in high and moderate risk networks.

The demand for transportation among urban residents in China is increasing in tandem with the nation’s population growth, rising consumption levels, and increasing car ownership rates. Breaking the existing high-carbon travel practices and reshaping positive low-carbon awareness represents an inevitable way to change existing transportation structures and reduce urban traffic congestion and carbon emissions. A mediating effect model was employed and we found that community satisfaction is an essential variable in the effect of traffic accessibility and travel behavior on low-carbon awareness. First, the impact of residents’ zero and low-carbon actions on their low-carbon awareness is mediated by community satisfaction. Furthermore, compared to high-income groups, community satisfaction exerts a robust mediating influence on low-income groups. The mediating effect of community satisfaction on the relationship between residential proximity to commercial centers and low-carbon awareness among individuals with low incomes is evident. Based on these findings, this paper explores the heterogeneity and associated measures of low-carbon awareness among residents. The conclusion of this study provides suggestions to promote residents’ low-carbon awareness by improving their travel experience from the perspective of community construction, providing scientific reference and a basis for the formulation of transportation policies for low-carbon city construction.

The ridge–furrow planting pattern is an effective strategy to improve grain yield, and changes in the ridge and furrow microenvironments affect wheat yield. However, the mechanism by which wheat yields are increased at different ridge–furrow ratios is unclear. In this study, four planting modes, namely the traditional planting mode (M1) and ridge–furrow ratios of 50:50 cm (M2), 75:50 cm (M3), and 100:50 cm (M4), were established for wheat under field conditions from 2021 to 2023; the effects of different treatments on light energy utilization, dry matter accumulation and transport, and grain yield were studied. The findings demonstrated that the M3 treatment exhibited the highest enhancements in parameters such as leaf area index (LAI), canopy photosynthetically effective radiation interception rate, relative chlorophyll content (SPAD) index, and net photosynthetic rate. Moreover, the M3 treatment displayed superior grain filling compared to other treatments. The post-anthesis assimilate accumulation in the M3 treatment was 11.93%, 4.69%, and 13.13% higher than that of M1, M2, and M4 treatments, respectively, and the grain yield in M3 increased by 7.70–9.56%, 3.13–4.91%, and 8.69–10.90% compared with those in M1, M2, and M4 in the two growing seasons, respectively. In summary, under the conditions of this study, the M3 treatment led to higher LAI and SPAD values in flag leaves post-anthesis compared to the other treatments. Moreover, M3 optimized canopy structure, led to the highest canopy interception rate, and increased photosynthetic rates per individual plant. Consequently, there was a significant increase in post-anthesis dry matter accumulation, resulting in the highest grain yield achieved among the treatments.

As one of the most densely populated, economically developed, and outwardly open urban agglomerations in China, the Pearl River Delta (PRD) urban agglomeration is a key player in achieving China’s carbon peak and carbon neutrality targets. This study analyzes low-emission development by examining the evolutionary patterns of carbon dioxide (CO2) emissions and the decoupling relationship between economic growth and CO2 emissions, using the latest available data from 2000 to 2020. Here are the main findings: (1) We found a significant fluctuation in the decoupling statuses between economic advancements and CO2 emissions within the PRD domain. Predominantly, a weak decoupling scenario was observed, where economic proliferations were paralleled by nearly equivalent increments in CO2 emissions. (2) The growth rate of carbon emissions increased significantly relative to economic expansion during 2015–2020, especially pronounced in cities such as Guangdong, Zhuhai, Foshan, and Dongguan. This delineates the persistent challenges in steering towards a pathway of energy conservation and emission abatement in the region. (3) Furthermore, a differential role of elasticity factors was noted across cities: Guangzhou and Shenzhen witnessed a significant influence of energy-saving elasticity in fostering a decoupling between economic surge and CO2 emissions, whereas in other cities, the emphasis shifted towards emission-reduction elasticity as a more vital determinant. The results of this study are of great significance for guiding policy makers and stakeholders in urban clusters across China and in similar regions globally to achieve low carbon development goals.

Abstract Background Cultivated peanut (Arachis hypogaea, AABB genome), an allotetraploid from a cross between A. duranensis (AA genome) and A. ipaensis (BB genome), is an important oil and protein crop with released genome and RNA-seq sequence datasets. These datasets provide the molecular foundation for studying gene expression and evolutionary patterns. However, there are no reports on the proteomic data of A. hypogaea cv. Tifrunner, which limits understanding of its gene function and protein level evolution. Results This study sequenced the A. hypogaea cv. Tifrunner leaf and root proteome using the tandem mass tag technology. A total of 4803 abundant proteins were identified. The 364 differentially abundant proteins were estimated by comparing protein abundances between leaf and root proteomes. The differentially abundant proteins enriched the photosystem process. The number of biased abundant homeologs between the two sub-genomes A (87 homeologs in leaf and root) and B (69 and 68 homeologs in leaf and root, respectively) was not significantly different. However, homeologous proteins with biased abundances in different sub-genomes enriched different biological processes. In the leaf, homeologs biased to sub-genome A enriched biosynthetic and metabolic process, while homeologs biased to sub-genome B enriched iron ion homeostasis process. In the root, homeologs with biased abundance in sub-genome A enriched inorganic biosynthesis and metabolism process, while homeologs with biased abundance in sub-genome B enriched organic biosynthesis and metabolism process. Purifying selection mainly acted on paralogs and homeologs. The selective pressure values were negatively correlated with paralogous protein abundance. About 77.42% (24/31) homeologous and 80% (48/60) paralogous protein pairs had asymmetric abundance, and several protein pairs had conserved abundances in the leaf and root tissues. Conclusions This study sequenced the proteome of A. hypogaea cv. Tifrunner using the leaf and root tissues. Differentially abundant proteins were identified, and revealed functions. Paralog abundance divergence and homeolog bias abundance was elucidated. These results indicate that divergent abundance caused retention of homologs in A. hypogaea cv. Tifrunner.

IntroductionEndometrial cancer is currently one of the three most common female reproductive cancers, which seriously threatens women’s lives and health. Hypoxia disrupts the tumor microenvironment, thereby affecting tumor progression and drug resistance.MethodsWe established hypoxia-related gene model to predict patient prognosis and 1-, 3-, and 5-year overall survival rates. Then, the expression level of hypoxia-related genes and survival data were extracted for comprehensive analysis by Cox regression analysis, and the model was established.ResultsWe analyzed the survival and prognosis of patients in the high and low-risk groups. The Kaplan-Meier curve showed that the low-risk group is associated with a better survival rate. The 1-, 3-, and 5-year AUC values of the model were 0.680, 0.698, and 0.687, respectively. Finally, we found that LAG3 may be a potential immune checkpoint for endometrial cancer.ConclusionWe found four hypoxia-related genes (ANXA2, AKAP12, NR3C1, and GPI) associated with prognosis. The hypoxia-related gene model can also predict prognosis and tumor microenvironment in endometrial cancer.

As the global COVID-19 pandemic continues and new SARS-CoV-2 variants of concern emerge, vaccines remain an important tool for preventing the pandemic. The inactivated or subunit vaccines themselves generally exhibit low immunogenicity, which needs adjuvants to improve the immune response. We previously developed a receptor binding domain (RBD)-targeted and self-assembled nanoparticle to elicit a potent immune response in both mice and rhesus macaques. Herein, we further improved the RBD production in the eukaryote system by in situ Crispr/Cas9-engineered CHO cells. By comparing the immune effects of various Toll-like receptor-targeted adjuvants to enhance nanoparticle vaccine immunization, we found that Pam2CSK4, a TLR2/6 agonist, could mostly increase the titers of antigen-specific neutralizing antibodies and durability in humoral immunity. Remarkably, together with Pam2CSK4, the RBD-based nanoparticle vaccine induced a significant Th1-biased immune response and enhanced the differentiation of both memory T cells and follicular helper T cells. We further found that Pam2CSK4 upregulated migration genes and many genes involved in the activation and proliferation of leukocytes. Our data indicate that Pam2CSK4 targeting TLR2, which has been shown to be effective in tuberculosis vaccines, is the optimal adjuvant for the SARS-CoV-2 nanoparticle vaccine, paving the way for an immediate clinical trial.

Abstract Background Isopsoralen (IPRN), one of the active ingredients of Psoralea corylifolia Linn, has anti-inflammatory properties. We attempted to investigate the inhibitory effects of IPRN on rheumatoid arthritis (RA) and characterize its potential mechanism. Methods RA fibroblast-like synoviocytes (FLSs) and mice with collagen-induced arthritis (CIA) were used as in vitro and in vivo models to analyze the antiarthritic effect of IPRN. Histological analysis of the inflamed joints from mice with CIA was performed using microcomputed tomography (micro-CT) and hematoxylin-eosin (HE) staining. RNA sequencing (RNA-Seq), network pharmacology analysis, molecular docking, drug affinity responsive target stability (DARTS) assay, and cellular thermal shift assay (CETSA) were performed to evaluate the targets of IPRN. Results IPRN ameliorated the inflammatory phenotype of RA FLSs by inhibiting their cytokine production, migration, invasion, and proangiogenic ability. IPRN also significantly reduced the severity of CIA in mice by decreasing paw thickness, arthritis score, bone damage, and serum inflammatory cytokine levels. A mechanistic study demonstrated that macrophage migration inhibitory factor (MIF), a key protein in the inflammatory process, was the specific target by which IPRN exerted its anti-inflammatory effects in RA FLSs. Conclusion Our study demonstrates the antiarthritic effect of IPRN, which suggests the therapeutic potential of IPRN in RA.

Abstract Background Consolidated bioprocessing (CBP) technique is a promising strategy for biorefinery construction, producing bulk chemicals directly from plant biomass without extra hydrolysis steps. Fixing and channeling CO2 into carbon metabolism for increased carbon efficiency in producing value-added compounds is another strategy for cost-effective bio-manufacturing. It has not been reported whether these two strategies can be combined in one microbial platform. Results In this study, using the cellulolytic thermophilic fungus Myceliophthora thermophila, we designed and constructed a novel biorefinery system DMCC (Direct microbial conversion of biomass with CO2 fixation) through incorporating two CO2 fixation modules, PYC module and Calvin–Benson–Bassham (CBB) pathway. Harboring the both modules, the average rate of fixing and channeling 13CO2 into malic acid in strain CP51 achieved 44.4, 90.7, and 80.7 mg/L/h, on xylose, glucose, and cellulose, respectively. The corresponding titers of malic acid were up to 42.1, 70.4, and 70.1 g/L, respectively, representing the increases of 40%, 10%, and 7%, respectively, compared to the parental strain possessing only PYC module. The DMCC system was further improved by enhancing the pentose uptake ability. Using raw plant biomass as the feedstock, yield of malic acid produced by the DMCC system was up to 0.53 g/g, with 13C content of 0.44 mol/mol malic acid, suggesting DMCC system can produce 1 t of malic acid from 1.89 t of biomass and fix 0.14 t CO2 accordingly. Conclusions This study designed and constructed a novel biorefinery system named DMCC, which can convert raw plant biomass and CO2 into organic acid efficiently, presenting a promising strategy for cost-effective production of value-added compounds in biorefinery. The DMCC system is one of great options for realization of carbon neutral economy.

The key enzyme 6-phosphofructo-2-kinase (PFK2)/fructose-2,6-bisphosphatase (FBPase-2) is responsible for regulating the rates of glycolysis and gluconeogenesis in eukaryotes. However, its functions and mechanisms in filamentous fungi remain largely enigmatic. In this study, we systematically investigated the function of this enzyme in Myceliophthora thermophila, a thermophilic filamentous fungus with great capacity to produce industrial enzymes and organic acids. Our results showed that the M. thermophila genome encodes three isomers, all with the PFK2/FBPase-2 structure: pfk2-a, pfk2-b, and pfk2-c. Overexpression of each gene revealed that endogenous expression of pfk2-c (PFK2 activity) promoted glucose metabolism, while overexpression of pfk2-a (FBPase-2 activity) inhibited strain growth. Using knockouts, we found that each gene was individually non-essential, but the triple knockout led to significantly slower growth compared with the wild-type strain. Only the pfk2-a single knockout exhibited 22.15% faster sugar metabolism, exerted through activation of 6-phosphofructo-1-kinase (PFK1), thereby significantly promoting glycolysis and the tricarboxylic acid cycle. The FBPase-2 deletion mutant strain also exhibited overflow metabolism, and knocking out pfk2-a was proved to be able to improve the production and synthesis rate of various metabolites, such as glycerol and malate. This is the first study to systematically investigate the function of PFK2/FBPase-2 in a thermophilic fungus, providing an effective target for metabolic engineering in filamentous fungi.

BackgroundThe cognitive level of post-stroke aphasia (PSA) patients is generally lower than non-aphasia patients, and cognitive impairment (CI) affects the outcome of stroke. However, for different types of PSA, what kind of cognitive assessment methods to choose is not completely clear. We investigated the Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), and the Non-language-based Cognitive Assessment (NLCA) to observe the evaluation effect of CI in patients with fluent aphasia (FA) and non-fluent aphasia (NFA).Methods92 stroke patients were included in this study. Demographic and clinical data of the stroke group were documented. The language and cognition were evaluated by Western Aphasia Battery (WAB), MoCA, MMSE, and NLCA. PSA were divided into FA and NFA according to the Chinese aphasia fluency characteristic scale. Pearson’s product–moment correlation coefficient test and multiple linear regression analysis were performed to explore the relationship between the sub-items of WAB and cognitive scores. The classification rate of CI was tested by Pearson’s Chi-square test or Fisher’s exact test.ResultsThe scores of aphasia quotient (AQ), MoCA, MMSE, and NLCA in NFA were lower than FA. AQ was positively correlated with MoCA, MMSE, and NLCA scores. Stepwise multiple linear regression analysis suggested that naming explained 70.7% of variance of MoCA and 79.9% of variance of MMSE; comprehension explained 46.7% of variance of NLCA. In the same type of PSA, there was no significant difference in the classification rate. The classification rate of CI in NFA by MoCA and MMSE was higher than that in FA. There was no significant difference in the classification rate of CI between FA and NFA by NLCA.ConclusionMoCA, MMSE, and NLCA can be applied in FA. NLCA is recommended for NFA.

Cuproptosis is the most recently discovered mode of cell death. It could affect the metabolism of cancer cells and surrounding infiltrating immune cells. In recent years, many studies have also shown that the tumor microenvironment (TME) plays a critical role in tumor growth and development. Mounting evidence suggests that Cuproptosis would bring unique insights into the development of pharmacological and nonpharmacological therapeutic techniques for cancer prevention and therapy. However, no study has been done on the combination of cuproptosis and TME in any cancer. Herein, we investigated the relationship between cuproptosis-related genes (CRGs), TME, and the prognosis of patients with Uterine Corpus Endometrial Carcinoma (UCEC). We identified three CRGs clusters based on 10 CRGs and three CRGs gene clusters based on 600 differentially expressed genes (DEGs) with significant prognostic differences. Following that, the CRGs score based on DEGs with significant prognostic differences was established to evaluate the prognosis and immunotherapeutic efficacy of UCEC patients. The CRGs score was shown to be useful in predicting clinical outcomes. Patients with a low CRGs score seemed to have a better prognosis, a better immunotherapeutic response, and a higher tumor mutation burden (TMB). In conclusion, our study explored the influence of cuproptosis patterns and TME on the prognosis of cancer patients, thereby improving their prognosis.

During the winter half-year (previous October–April), the mid-latitude westerlies flows around the Tibetan Plateau (TP) and generate a dynamic low-pressure trough on its south side and a high-pressure ridge on its north side. In this study, we define the vorticity perturbation as the difference between local vorticity and the meridionally-averaged vorticity. Then, the difference of averaged vorticity perturbation at 600 hPa in the two key areas where the trough and ridge are located is used to represent the intensity of the flows around the Tibetan Plateau (FAT). The evolution characteristics of FAT in the winter half-year, as well as in autumn, winter and spring, are analyzed. Moreover, under global warming, in winter the relationship of FAT to the precipitation and temperature in China are discussed. The results show that FAT steadily exists on both sides of TP during the winter half-year. With the north-south migration of the mid-latitude westerlies, the FAT gradually strengthens in autumn, with the strongest intensity and the widest range in winter, and begins to weaken in spring. The intensity of FAT (IFAT) has a decreasing trend and a quasi-4a period variation on the interannual scale in all the time, both of which are closely related to the mid-latitude westerlies upstream of TP. Represented by the winter when IFAT is strongest, the IFAT is significantly correlated to the change of precipitation and temperature in most parts of China under global warming, especially in the convergence area over central-eastern China. There is also a significant correlation between IFAT and the precipitation and temperature anomalies in Northwest China, TP, and Northeast China. This relationship between the FAT anomaly and the climate anomaly in China in winter can be well explained by analyzing the anomalies of large-scale circulation, outgoing longwave radiation and water vapor flux divergence. The FAT anomaly maybe one of the reasons for the climate extreme events in China in winter.

Stromatolites, among the earliest fossils in Earth’s history, are widely distributed on the margins of the North China Precambrian carbonate platform. The formation processes of stromatolites reveal the biomineralization and evolution of early life in the Precambrian. The well-preserved stromatolitic dolostones recorded in the Ganjingzi Formation are developed around Yuanjiagou village, in southern Liaoning Province. The morphology of the Ganjingzi stromatolites manifests in stratiform, columnar, and domal forms. A tripartite lamina structure including light laminae and two types of dark laminae is observed in thin sections. The origins of dark laminae were related to microbial metabolism, while the light laminae were the result of the recrystallization of synsedimentary marine cement. Hardground substrate and carbonate fragments were suitable for microbes to colonize, suggesting that microbes can adapt to various current energy settings. A comparison of the growth environment, morphology, and laminae features between the Ganjingzi stromatolites and modern carbonate stromatolites from Hamelin Pool and Lagoa Vermelha suggest that the Ganjingzi stromatolites may have been formed in a restricted tidal-flat setting with high salinity and evaporation. The role of microbes that form modern stromatolites in inducing precipitation of carbonate or binding sediments, might contribute to the formation of the Ganjingzi stromatolites. The formation process of the Ganjingzi stromatolites indicates that the microbial communities, favorable substrate, and synsedimentary marine cement were the key factors in promoting the development of the Neoproterozoic stromatolites on the northeastern margin of the North China Craton.

Although there have been many discussions about the influencing factors of urban expansion, the heterogeneity of the driving mechanisms behind urban form remains poorly understood. Therefore, this paper evaluated the heterogeneous impacts of potential determinants on urban form, considering regional disparities and the stage of development. Based on land use data collected from Landsat ETM and TM scenes, the landscape metrics of urban size, urban centrality, urban shape irregularity, and urban fragmentation were measured to describe the urban form of 265 Chinese cities. We find that the regional disparities and development-stage variations significantly affect urban form. All urban form variables showed a significant stair-stepping difference in cities at various development stages, indicating that as a city upgrades its level of development, the intensity of urban expansion gradually increases, the shape of the urban edge becomes more fragmented and the urban built-up area becomes more compact. Urban form in Chinese cities shows significant geographical heterogeneity in terms of its driving forces. The effect of the socioeconomic factors on urban form also presented changes depending on the development stage. Our results provide helpful references for policymakers within urban spatial structure planning and land resource management.

Accurate analysis of technological innovation mechanism in different regions is the key to promoting China’s technological innovation, economic transformation and upgrading. This paper collected statistical data of high-tech enterprises in 27 provinces in China from 2009 to 2016, established a novel PSO-GRNN model, and applied sensitivity analysis to explore the influencing factors and regional differences of enterprise technological innovation in Eastern, Central and Western China. The empirical results showed that the influencing factors were innovation investment, market environment, government support and foreign technology spillover sorting by impact size. Innovation investment was the decisive factor of technological innovation, but innovation resources mainly concentrated on Eastern China, severely insufficient in Central and Western China. Market environment was favorable to Eastern and Central China, but unfavorable to Western China, which restricted greatly the development of Western China. The principalagent problem of state-owned enterprise and the crowding out effect of government research and development funds jointly led to the negative influence of government support on technological innovation. Foreign technology spillover had significant positive effects on technological innovation in Western China. This paper clarifies some disputes about influencing factors of technological innovation and provides a new research perspective for related issues. First published online 27 May 2021

Methyl gallate (MG), a polyphenolic compound found in plants, is widely used in traditional Chinese medicine. MG is known to alleviate several cancer symptoms. However, most studies that have reported the antitumor effects of MG have done so at the cellular level, and the inhibitory effect and therapeutic mechanism of MG in hepatocellular carcinoma (HCC) have not been extensively explored in vivo. We aimed to understand the therapeutic mechanism of MG in HCC in vitro and in vivo. MTT and colony formation assays were used to determine the impact of MG on the proliferation of a human HCC cell line, BEL-7402; wound healing and transwell assays were used to quantify the migration and invasion of HCC cells. Western blotting was used to quantify the expression of the AMPK/NF-κB signaling pathway proteins. In vivo tumor growth was measured in a xenograft tumor nude mouse model treated with MG, and hematoxylin–eosin staining and immunohistochemistry (IHC) were used to visualize the histological changes in the tumor tissue. We found that MG showed anti-proliferative effects both in vitro and in vivo. MG downregulated the protein expression of AMPK, NF-κB, p-NF-κB, and vimentin and upregulated the expression of E-cadherin in a dose-dependent manner. Additionally, MG inhibited the migration and invasion of HCC cells by decreasing MMP9 and MMP2 expression and increasing TIMP-2 expression. These were consistent with the results of IHC in vivo. MG inhibited the proliferation, migration, and invasion of HCC cells. This effect potentially involves the regulation of the AMPK/NF-κB pathway, which in turn impacts epithelial-mesenchymal transition and MMP expression.