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Abstract Sirtuins, which are NAD+-dependent class III histone deacetylases, are involved in various biological processes, including DNA damage repair, immune inflammation, oxidative stress, mitochondrial homeostasis, autophagy, and apoptosis. Sirtuins are essential regulators of cellular function and organismal health. Increasing evidence suggests that the development of age-related diseases, including kidney diseases, is associated with aberrant expression of sirtuins, and that regulation of sirtuins expression and activity can effectively improve kidney function and delay the progression of kidney disease. In this review, we summarise current studies highlighting the role of sirtuins in renal diseases. First, we discuss sirtuin family members and their main mechanisms of action. We then outline the possible roles of sirtuins in various cell types in kidney diseases. Finally, we summarise the compounds that activate or inhibit sirtuin activity and that consequently ameliorate renal diseases. In conclusion, targeted modulation of sirtuins is a potential therapeutic strategy for kidney diseases. Video Abstract

Abstract Background The interest in targeted cancer therapies has been growing rapidly. While numerous cancer biomarkers and targeted treatment strategies have been developed and employed, there are still significant limitations and challenges in the early diagnosis and targeted treatment of cancers. Accordingly, there is an urgent need to identify novel targets and develop new targeted drugs. Methods The study was conducted using combined cis-Mendelian randomization (cis-MR) and colocalization analysis. We analyzed data from 732 plasma proteins to identify potential drug targets associated with eight site-specific cancers. These findings were further validated using the UK Biobank dataset. Then, a protein–protein interaction network was also constructed to examine the interplay between the identified proteins and the targets of existing cancer medications. Results This MR analysis revealed associations between five plasma proteins and prostate cancer, five with breast cancer, and three with lung cancer. Subsequently, these proteins were classified into four distinct target groups, with a focus on tier 1 and 2 targets due to their higher potential to become drug targets. Our study indicatied that genetically predicted KDELC2 (OR: 0.89, 95% CI 0.86–0.93) and TNFRSF10B (OR: 0.74, 95% CI 0.65–0.83) are inversely associated with prostate cancer. Furthermore, we observed an inverse association between CPNE1 (OR: 0.96, 95% CI 0.94–0.98) and breast cancer, while PDIA3 (OR: 1.19, 95% CI 1.10–1.30) were found to be associated with the risk of breast cancer. In addition, we also propose that SPINT2 (OR: 1.05, 95% CI 1.03–1.06), GSTP1 (OR: 0.82, 95% CI 0.74–0.90), and CTSS (OR: 0.91, 95% CI 0.88–0.95) may serve as potential therapeutic targets in prostate cancer. Similarly, GDI2 (OR: 0.85, 95% CI 0.80–0.91), ISLR2 (OR: 0.87, 95% CI 0.82–0.93), and CTSF (OR: 1.14, 95% CI 1.08–1.21) could potentially be targets for breast cancer. Additionally, we identified SFTPB (OR: 0.93, 95% CI 0.91–0.95), ICAM5 (OR: 0.95, 95% CI 0.93–0.97), and FLRT3 (OR: 1.10, 95% CI 1.05–1.15) as potential targets for lung cancer. Notably, TNFRSF10B, GSTP1, and PDIA3 were found to interact with the target proteins of current medications used in prostate or breast cancer treatment. Conclusions This comprehensive analysis has highlighted thirteen plasma proteins with potential roles in three site-specific cancers. Continued research in this area may reveal their therapeutic potential, particularly KDELC2, TNFRSF10B, CPNE1, and PDIA3, paving the way for more effective cancer treatments.

BackgroundAs a damage-associated molecular pattern protein, high mobility group box 1 (HMGB1) is associated with kidney and systemic inflammation. The predictive and therapeutic value of HMGB1 as a biomarker has been confirmed in various diseases. However, its value in diabetic kidney disease (DKD) remains unclear. Therefore, this study aimed to investigate the correlation between serum and urine HMGB1 levels and DKD progression.MethodsWe recruited 196 patients with type 2 diabetes mellitus (T2DM), including 109 with DKD and 87 T2DM patients without DKD. Additionally, 60 healthy participants without T2DM were also recruited as controls. Serum and urine samples were collected for HMGB1 analysis. Simultaneously, tumor necrosis factor receptor superfamily member 1A (TNFR-1) in serum and kidney injury molecule (KIM-1) in urine samples were evaluated for comparison.ResultsSerum and urine HMGB1 levels were significantly higher in patients with DKD than in patients with T2DM and healthy controls. Additionally, serum HMGB1 levels significantly and positively correlated with serum TNFR-1 (R2 = 0.567, p

BackgroundThe association of gut microbiota (GM) and chronic kidney disease (CKD), and the relevancy of GM and chronic systemic inflammation in CKD, were revealed on the basis of researches on gut–kidney axis in previous studies. However, their causal relationships are still unclear.ObjectiveTo uncover the causal relationships between GM and CKD, as well as all known GM from eligible statistics and chronic systemic inflammation in CKD, we performed two-sample Mendelian randomization (MR) analysis.Materials and methodsWe acquired the latest and most comprehensive summary statistics of genome-wide association study (GWAS) from the published materials of GWAS involving GM, CKD, estimated glomerular filtration rate (eGFR), c-reactive protein (CRP) and urine albumin creatine ratio (UACR). Subsequently, two-sample MR analysis using the inverse-variance weighted (IVW) method was used to determine the causality of exposure and outcome. Based on it, additional analysis and sensitivity analysis verified the significant results, and the possibility of reverse causality was also assessed by reverse MR analysis during this study.ResultsAt the locus-wide significance threshold, IVW method and additional analysis suggested that the protective factors for CKD included family Lachnospiraceae (P=0.049), genus Eubacterium eligens group (P=0.002), genus Intestinimonas (P=0.009), genus Streptococcu (P=0.003) and order Desulfovibrionales (P=0.001). Simultaneously, results showed that genus LachnospiraceaeUCG010 (P=0.029) was a risk factor for CKD. Higher abundance of genus Desulfovibrio (P=0.048) was correlated with higher eGFR; higher abundance of genus Parasutterella (P=0.018) was correlated with higher UACR; higher abundance of class Negativicutes (P=0.003), genus Eisenbergiella (P=0.021), order Selenomonadales (P=0.003) were correlated with higher CRP levels; higher abundance of class Mollicutes (0.024), family Prevotellaceae (P=0.030), phylum Tenericutes (P=0.024) were correlated with lower levels of CRP. No significant pleiotropy or heterogeneity was found in the results of sensitivity analysis, and no significant causality was found in reverse MR analysis.ConclusionThis study highlighted associations within gut-kidney axis, and the causal relationships between GM and CKD, as well as GM and chronic systemic inflammation in CKD were also revealed. Meanwhile, we expanded specific causal gut microbiota through comprehensive searches. With further studies for causal gut microbiota, they may have the potential to be new biomarkers for targeted prevention of CKD and chronic systemic inflammation in CKD.

Sirtuins are a family of NAD+ III-dependent histone deacetylases that consists of seven family members, Sirt1-Sirt7, which regulate various signalling pathways and are involved in many critical biological processes of kidney diseases. Traditional Chinese medicine (TCM), as an essential part of the global healthcare system, has multi-component and multi-pathway therapeutic characteristics and plays a role in preventing and controlling various diseases. Through ongoing collaboration with modern medicine, TCM has recently achieved many remarkable advancements in theoretical investigation, mechanistic research, and clinical applications related to kidney diseases. Therefore, a comprehensive and systematic summary of TCM that focuses on sirtuins as the intervention target for kidney diseases is necessary. This review introduces the relationship between abnormal sirtuins levels and common kidney diseases, such as diabetic kidney disease and acute kidney injury. Based on the standard biological processes, such as inflammation, oxidative stress, autophagy, mitochondrial homeostasis, and fibrosis, which are underlying kidney diseases, comprehensively describes the roles and regulatory effects of TCM targeting the sirtuins family in various kidney diseases.

Diabetic kidney disease (DKD) is a major microvascular complication of diabetes and a leading cause of end-stage renal disease worldwide. Autophagy plays an important role in maintaining cellular homeostasis in renal physiology. In DKD, the accumulation of advanced glycation end products induces decreased renal autophagy-related protein expression and transcription factor EB (TFEB) nuclear transfer, leading to impaired autophagy and lysosomal function and blockage of autophagic flux. This accelerates renal resident cell injury and apoptosis, mediates macrophage infiltration and phenotypic changes, ultimately leading to aggravated proteinuria and fibrosis in DKD. Natural polyphenols show promise in treating DKD by regulating autophagy and promoting nuclear transfer of TFEB and lysosomal repair. This review summarizes the characteristics of autophagy in DKD, and the potential application and mechanisms of some known natural polyphenols as autophagy regulators in DKD, with the goal of contributing to a deeper understanding of natural polyphenol mechanisms in the treatment of DKD and promoting the development of their applications. Finally, we point out the limitations of polyphenols in current DKD research and provide an outlook for their future research.

Diabetic nephropathy (DN) often leads to end-stage renal disease. Oxidative stress demonstrates a crucial act in the onset and progression of DN, which triggers various pathological processes while promoting the activation of inflammation and forming a vicious oxidative stress-inflammation cycle that induces podocyte injury, extracellular matrix accumulation, glomerulosclerosis, epithelial-mesenchymal transition, renal tubular atrophy, and proteinuria. Conventional treatments for DN have limited efficacy. Polyphenols, as antioxidants, are widely used in DN with multiple targets and fewer adverse effects. This review reveals the oxidative stress and oxidative stress-associated inflammation in DN that led to pathological damage to renal cells, including podocytes, endothelial cells, mesangial cells, and renal tubular epithelial cells. It demonstrates the potent antioxidant and anti-inflammatory properties by targeting Nrf2, SIRT1, HMGB1, NF-κB, and NLRP3 of polyphenols, including quercetin, resveratrol, curcumin, and phenolic acid. However, there remains a long way to a comprehensive understanding of molecular mechanisms and applications for the clinical therapy of polyphenols.

BackgroundTherapeutic approaches that target the gut microbiota (GM) may be helpful in the potential prevention and treatment of IgA nephropathy (IgAN). Meanwhile, relevant studies demonstrated a correlation between GM and IgAN, however, these confounding evidence cannot prove a causal relationship between GM and IgAN.MethodsBased on the data from the GM genome-wide association study (GWAS) of MiBioGen and the IgAN GWAS data from the FinnGen research. A bi-directional Mendelian randomization (MR) study was performed to explore the causal relationship between GM and IgAN. We used inverse variance weighted (IVW) method as the primary method to determine the causal relationship between exposure and outcome in our MR study. Besides, we used additional analysis (MR-Egger, weighted median) and sensitivity analysis (Cochrane’s Q test, MR-Egger and MR-PRESSO) to select significant results, followed by Bayesian model averaging (MR-BMA) to test the results of MR study. Finally, a reverse MR analysis was conducted to estimate the probability of reverse causality.ResultsAt the locus-wide significance level, the results of IVW method and additional analysis showed that Genus Enterorhabdus was a protective factor for IgAN [OR: 0.456, 95% CI: 0.238-0.875, p=0.023], while Genus butyricicoccus was a risk factor for IgAN [OR: 3.471, 95% CI: 1.671-7.209, p=0.0008]. In the sensitivity analysis, no significant pleiotropy or heterogeneity of the results was found.ConclusionOur study revealed the causal relationship between GM and IgAN, and expanded the variety of bacterial taxa causally related to IgAN. These bacterial taxa could become novel biomarkers to facilitate the development of targeted therapies for IgAN, developing our understanding of the “gut-kidney axis”.

Artemisinin, an antimalarial traditional Chinese herb, is isolated from Artemisia annua. L, and has shown fewer side effects. Several pieces of evidence have demonstrated that artemisinin and its derivatives exhibited therapeutic effects on diseases like malaria, cancer, immune disorders, and inflammatory diseases. Additionally, the antimalarial drugs demonstrated antioxidant and anti-inflammatory activities, regulating the immune system and autophagy and modulating glycolipid metabolism properties, suggesting an alternative for managing kidney disease. This review assessed the pharmacological activities of artemisinin. It summarized the critical outcomes and probable mechanism of artemisinins in treating kidney diseases, including inflammatory, oxidative stress, autophagy, mitochondrial homeostasis, endoplasmic reticulum stress, glycolipid metabolism, insulin resistance, diabetic nephropathy, lupus nephritis, membranous nephropathy, IgA nephropathy, and acute kidney injury, suggesting the therapeutic potential of artemisinin and its derivatives in managing kidney diseases, especially the podocyte-associated kidney diseases.

Podocyte injury is a major cause of proteinuria in kidney diseases, and persistent loss of podocytes leads to rapid irreversible progression of kidney disease. Sirtuins, a class of nicotinamide adenine dinucleotide-dependent deacetylases, can promote DNA repair, modify transcription factors, and regulate the cell cycle. Additionally, sirtuins play a critical role in renoprotection, particularly against podocyte injury. They also have pleiotropic protective effects on podocyte injury-related glomerular diseases, such as improving the immune inflammatory status and oxidative stress levels, maintaining mitochondrial homeostasis, enhancing autophagy, and regulating lipid metabolism. Sirtuins deficiency causes podocyte injury in different glomerular diseases. Studies using podocyte sirtuin-specific knockout and transgenic models corroborate this conclusion. Of note, sirtuin activators have protective effects in different podocyte injury-related glomerular diseases, including diabetic kidney disease, focal segmental glomerulosclerosis, membranous nephropathy, IgA nephropathy, and lupus nephritis. These findings suggest that sirtuins are promising therapeutic targets for preventing podocyte injury. This review provides an overview of recent advances in the role of sirtuins in kidney diseases, especially their role in podocyte injury, and summarizes the possible rationale for sirtuins as targets for pharmacological intervention in podocyte injury-related glomerular diseases.

Podocyte injury is a common cause of proteinuric kidney diseases. Uncontrollable progressive podocyte loss accelerates glomerulosclerosis and increases the risk of end-stage renal disease. To date, owing to the complex pathological mechanism, effective therapies for podocyte injury have been limited. Accumulating evidence supports the indispensable role of autophagy in the maintenance of podocyte homeostasis. A variety of natural compounds and their derivatives have been found to regulate autophagy through multiple targets, including promotes nuclear transfer of transcription factor EB and lysosomal repair. Here, we reviewed the recent studies on the use of natural compounds and their derivatives as autophagy regulators and discussed their potential applications in ameliorating podocyte injury. Several known natural compounds with autophagy-regulatory properties, such as quercetin, silibinin, kaempferol, and artemisinin, and their medical uses were also discussed. This review will help in improving the understanding of the podocyte protective mechanism of natural compounds and promote their development for clinical use.

Background: The pathogenesis and treatment of cardiovascular disease mediated by chronic kidney disease (CKD) are key research questions. Specifically, the mechanisms underlying the cardiorenal protective effect of Yiqi–Huoxue–Jiangzhuo formula (YHJF), a traditional Chinese herbal medicine, have not yet been clarified. Methods: A classical CKD mouse model was constructed by 5/6 nephrectomy (Nx) to study the effects of YHJF intervention on 5/6 Nx mice cardiorenal function, gut microbial composition, gut-derived metabolites, and NLRP3 inflammasome pathways. Results: YHJF improved cardiac dysfunction and reversed left ventricular hypertrophy, myocardial hypertrophy, and interstitial fibrosis in 5/6 Nx mice. In addition, YHJF inhibited activation of the NLRP3 inflammasome and downregulated the expression of TNF-α and IL-1β both in the heart and serum; reconstitution of the intestinal flora imbalance was also found in 5/6 Nx mice treated with YHJF. Spearman’s correlation and redundancy analyses showed that changes in the intestinal flora of 5/6 Nx mice were related to clinical phenotype and serum inflammatory levels. Conclusions: Treatment with YHJF effectively protected the heart function of 5/6 Nx mice; this effect was attributed to inhibition of NLRP3 inflammasome activation and regulation of intestinal microbial composition and derived metabolites. YHJF has potential for improving intestinal flora imbalance and gut-derived toxin accumulation in patients with CKD, thereby preventing cardiovascular complications.

Sirtuins, as regulators of metabolism and energy, have been found to play an important role in health and disease. Sirt1, the most widely studied member of the sirtuin family, can ameliorate oxidative stress, immune inflammation, autophagy, and mitochondrial homeostasis by deacetylating regulatory histone and nonhistone proteins. Notably, sirt1 has gradually gained attention in kidney disease research. Therefore, an evaluation of the overall distribution of publications concerning sirt1 based on bibliometric analysis methods to understand the thematic evolution and emerging research trends is necessary to discover topics with potential implications for kidney disease research. We conducted a bibliometric analysis of publications derived from the Web of Science Core Collection and found that publications concerning sirt1 have grown dramatically over the past 2 decades, especially in the past 5 years. Among these, the proportion of publications regarding kidney diseases have increased annually. China and the United States are major contributors to the study of sirt1, and Japanese researchers have made important contributions to the study of sirt1 in kidney disease. Obesity, and Alzheimer’s disease are hotspots diseases for the study of sirt1, while diabetic nephropathy is regarded as a research hotspot in the study of sirt1 in kidney disease. NAD+, oxidative stress, and p53 are the focus of the sirt1 research field. Autophagy and NLRP3 inflammasome are emerging research trends have gradually attracted the interest of scholars in sirt1, as well as in kidney disease. Notably, we also identified several potential research topics that may link sirt1 and kidney disease, which require further study, including immune function, metabolic reprogramming, and fecal microbiota.

Background: Podocyte injury has a direct causal relationship with proteinuria and glomerulosclerosis and, on a chronic level, can lead to irreversible disease progression. Podocyte injury plays a critically decisive role in the development of proteinuric kidney disease. In recent years, the research on podocyte injury has developed rapidly all over the world. However, no report has summarized the field of podocyte injury as a whole to date. Using bibliometric analysis, this study aimed to evaluate the current state of worldwide podocyte injury research in the last 30 years and identify important achievements, primary research fields, and emerging trends.Methods: Publications related to podocyte injury were retrieved from Web of Science Core Collection. HistCite, VOSviewer, CiteSpace, and the Bibliometrix Package were used for bibliometric analysis and visualization, including the analysis of the overall distribution of annual outputs, leading countries, active institutions and authors, core journals, co-cited references, and keywords. Total global citation score and total local citation score were used to assess the quality and impact of publications.Results: A total of 2,669 publications related to podocyte injury were identified. Publications related to podocyte injury tended to increase continuously. A total of 10,328 authors from 2,171 institutions in 69 countries published studies related to podocyte injury. China (39.46%) was the most prolific country, and the number of citations of studies in the United States (cited 36,896 times) ranked first. Moin A Saleem, John Cijiang He, and Zhihong Liu were the top three contributing authors, and Journal of the American Society of Nephrology and Kidney International were the most popular journals in the field. “Diabetic nephropathy” is the primary focus area of podocyte injury research, and “autophagy,” “microRNA,” and “inflammation” were the top keywords of emerging research hotspots, and traditional Chinese medicine monomer may be a neglected research gap.Conclusion: Our research found that global publications on podocyte injury have increased dramatically. Diabetic nephropathy is the main research field of podocyte injury, whereas autophagy, microRNA, and inflammation are the top topics getting current attention from scholars and which may become the next focus in podocyte injury research.

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.