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Abstract Advances in single-cell transcriptomics provide an unprecedented opportunity to explore complex biological processes. However, computational methods for analyzing single-cell transcriptomics still have room for improvement especially in dimension reduction, cell clustering, and cell–cell communication inference. Herein, we propose a versatile method, named DcjComm, for comprehensive analysis of single-cell transcriptomics. DcjComm detects functional modules to explore expression patterns and performs dimension reduction and clustering to discover cellular identities by the non-negative matrix factorization-based joint learning model. DcjComm then infers cell–cell communication by integrating ligand-receptor pairs, transcription factors, and target genes. DcjComm demonstrates superior performance compared to state-of-the-art methods.

Abstract Background The complex interplay between Sirtuin 1 (SIRT1) and FOXO3 in endometrial cancer (EC) remains understudied. This research aims to unravel the interactions of deacetylase SIRT1 and transcription factor FOXO3 in EC, focusing on their impact on mitophagy and hormone resistance. Methods High-throughput sequencing, cell experiments, and bioinformatics tools were employed to investigate the roles and interactions of SIRT1 and FOXO3 in EC. Co-immunoprecipitation (Co-IP) assay was used to assess the interaction between SIRT1 and FOXO3 in RL95-2 cells. Functional assays were used to assess cell viability, proliferation, migration, invasion, apoptosis, and the expression of related genes and proteins. A mouse model of EC was established to evaluate tumor growth and hormone resistance under different interventions. Immunohistochemistry and TUNEL assays were used to assess protein expression and apoptosis in tumor tissues. Results High-throughput transcriptome sequencing revealed a close association between SIRT1, FOXO3, and EC development. Co-IP showed a protein–protein interaction between SIRT1 and FOXO3. Overexpression of SIRT1 enhanced FOXO3 deacetylation and activity, promoting BNIP3 transcription and PINK1/Parkin-mediated mitophagy, which in turn promoted cell proliferation, migration, invasion, and inhibited apoptosis in vitro, as well as increased tumor growth and hormone resistance in vivo. These findings highlighted SIRT1 as an upstream regulator and potential therapeutic target in EC. Conclusion This study reveals a novel molecular mechanism underlying the functional relevance of SIRT1 in regulating mitophagy and hormone resistance through the deacetylation of FOXO3 in EC, thereby providing valuable insights for new therapeutic strategies.

Abstract Objective Femoral neck fractures (FNF) are known to have significant morbidity and mortality rates. Multiple chronic conditions (MCC) are defined as the presence of two or more chronic diseases that greatly affect the quality of life in older adults. The aim of this study is to explore the impact of MCC and Charlson comorbidity index (CCI) on surgical outcomes in patients with FNF. Methods Patients with FNF who underwent joint replacement surgery were selected for this study. Patients who had two or more diseases simultaneously were divided into two groups: the MCC group and the non-MCC (NMCC) group. The CCI was calculated to assess the severity of patients’ comorbidities in the MCC group. Baseline data, surgical details, and prognosis-related indicators were analyzed and compared between the two patient groups. Spearman correlation analysis was performed to assess the relationship between CCI and length of hospital stay, Harris score, skeletal muscle index (SMI), and age. Univariate and multivariate logistic regression analysis was conducted to identify the risk factors for mortality in FNF patients at 1 and 5 years after surgery. Results A total of 103 patients were included in the MCC group, while the NMCC group consisted of 40 patients. However, the patients in the MCC group were found to be older, had a higher incidence of sarcopenia, and lower SMI values (p

Abstract Objective To analyze the epidemic characteristics of common respiratory tract infection pathogens in children with respiratory tract infection, and provide scientific basis for the prevention and control of respiratory tract infection. Methods A retrospective collection of clinical data was conducted on 11,538 children with respiratory tract infections at Luoyang Maternal and Child Health Hospital from December 2022 to November 2023. The types of respiratory tract infections, including upper and lower respiratory tract infections, as well as five respiratory pathogens: influenza A virus (influenza A), influenza B virus (influenza B virus, adenovirus (ADV), respiratory syncytial virus (RSV), and Mycoplasma pneumoniae (MP) infections, were analyzed and compared for different genders, ages, temperatures, and air quality in different months; And the changes of five pathogens in children with respiratory tract infections of different disease severity. Results From December 2022 to November 2023, a total of 11,538 children with respiratory infections were included in the analysis, including 6436 males and 5102 females, with an age of 4.92 ± 2.03 years. The proportion of upper respiratory tract infections is as high as 72.17%, and lower respiratory tract infections account for 27.83%. Among them, 2387 were positive for Flu A antigen, with a positive rate of 20.69%, 51 cases were positive for Flu B antigen, and the positive rate was 0.4%, 1296 cases were positive for adv antigen, with a positive rate of 11.23%, 868 cases were positive for RSV antigen, with a positive rate of 7.52%, 2481 cases were positive for MP IgM antibody or MP antigen, and the positive rate was 21.50%. Flu B in male children The infection rate of ADV and MP was higher than that of female children (p 6 years was higher than that in children aged 0–3 years (p

Abstract The inference of cell–cell communication (CCC) is crucial for a better understanding of complex cellular dynamics and regulatory mechanisms in biological systems. However, accurately inferring spatial CCCs at single-cell resolution remains a significant challenge. To address this issue, we present a versatile method, called DeepTalk, to infer spatial CCC at single-cell resolution by integrating single-cell RNA sequencing (scRNA-seq) data and spatial transcriptomics (ST) data. DeepTalk utilizes graph attention network (GAT) to integrate scRNA-seq and ST data, which enables accurate cell-type identification for single-cell ST data and deconvolution for spot-based ST data. Then, DeepTalk can capture the connections among cells at multiple levels using subgraph-based GAT, and further achieve spatially resolved CCC inference at single-cell resolution. DeepTalk achieves excellent performance in discovering meaningful spatial CCCs on multiple cross-platform datasets, which demonstrates its superior ability to dissect cellular behavior within intricate biological processes.

Objective To explore the guiding value of thromboelastography (TEG) in the formulation of personalized anticoagulation regimen after knee arthroscopy. Methods A total of 50 patients who underwent knee arthroscopy in our hospital from April to August 2023 were randomly divided into two groups. Twenty-seven patients with routine anticoagulation were selected as the control group, and 23 patients with personalized anticoagulation were selected as the experimental group. Conventional anticoagulation was a prophylactic dose of low molecular weight heparin calcium (LMWHC) selected according to body weight, once a day to 7 days after surgery. Personalized anticoagulation was performed according to the prophylactic dose of LMWHC until postoperative day 3. On postoperative day 3, LMWHC was changed to aspirin according to the TEG return index (MA>70 mm, α Angle >72°, K value

Abstract High-grade B-cell lymphoma (HGBCL), the subtype of non-Hodgkin lymphoma, to be relapsed or refractory in patients after initial therapy or salvage chemotherapy. Dual dysregulation of MYC and BCL2 is one of the important pathogenic mechanisms. Thus, combined targeting of MYC and BCL2 appears to be a promising strategy. Dihydroorotate dehydrogenase (DHODH) is the fourth rate-limiting enzyme for the de novo biosynthesis of pyrimidine. It has been shown to be a potential therapeutic target for multiple diseases. In this study, the DHODH inhibitor brequinar exhibited growth inhibition, cell cycle blockade, and apoptosis promotion in HGBCL cell lines with MYC and BCL2 rearrangements. The combination of brequinar and BCL2 inhibitors venetoclax had a synergistic inhibitory effect on the survival of DHL cells through different pathways. Venetoclax could upregulate MCL-1 and MYC expression, which has been reported as a resistance mechanism of BCL2 inhibitors. Brequinar downregulated MCL-1 and MYC, which could potentially overcome drug resistance to venetoclax in HGBCL cells. Furthermore, brequinar could downregulate a broad range of genes, including ribosome biosynthesis genes, which might contribute to its anti-tumor effects. In vivo studies demonstrated synergetic tumor growth inhibition in xenograft models with brequinar and venetoclax combination treatment. These results provide preliminary evidence for the rational combination of DHODH and BCL2 blockade in HGBCL with abnormal MYC and BCL2.

Plants produce diverse flavonoids for defense and stress resistance, most of which have health benefits and are widely used as food additives and medicines. Methylation of the free hydroxyl groups of flavonoids, catalyzed by S-adenosyl-l-methionine-dependent O-methyltransferases (OMTs), significantly affects their physicochemical properties and bioactivities. Soybeans (Glycine max) contain a rich pool of O-methylated flavonoids. However, the OMTs responsible for flavonoid methylation in G. max remain largely unknown. We screened the G. max genome and obtained 22 putative OMT-encoding genes that share a broad spectrum of amino acid identities (25–96%); among them, 19 OMTs were successfully cloned and heterologously expressed in Escherichia coli. We used the flavonoids containing the free 3, 5, 7, 8, 3′, 4′ hydroxyl group, such as flavones (luteolin and 7, 8-dihydroxyflavone), flavonols (kaempferol and quercetin), flavanones (naringenin and eriodictyol), isoflavonoids (daidzein and glycetein), and caffeic acid as substrates, and 15 OMTs were proven to catalyze at least one substrate. The methylation activities of these GmOMTs covered the 3, 7, 8, 3′, 4′- hydroxyl of flavonoids and 7, 4′- hydroxyl of isoflavonoids. The systematic characterization of G. max flavonoid OMTs provides insights into the biosynthesis of methylated flavonoids in soybeans and OMT bioparts for the production of methylated flavonoids via synthetic biology.

Rapid acquisition of the kinematic deformation field and seismic intensity distribution of large earthquakes is crucial for postseismic emergency rescue, disaster assessment, and future seismic risk research. The advancement of GNSS observation and data processing makes it play an important role in this field, especially the high-frequency GNSS. We used the differential positioning method to calculate the 1 HZ GNSS data from 98 sites within 1000 km of the MS7.4 Maduo earthquake epicenter. The kinematic deformation field and the distribution of the seismic intensity by using the peak ground velocity derived from displacement waveforms were obtained. The results show that: 1) Horizontal coseismic response deformation levels ranging from 25 mm to 301 mm can be observed within a 1000 km radius from the epicenter. Coseismic response deformation on the east and west sides shows bilateral asymmetry, which markedly differs from the symmetry presented by surface rupture. 2) The seismic intensity obtained through high-frequency GNSS and field investigations exhibits good consistency of the scope and orientation in the high seismic intensity area, although the former is generally slightly smaller than the latter. 3) There may exist obstacles on the eastern side of the seismogenic fault. The Maduo earthquake induced a certain tectonic stress loading effect on the western Kunlun Pass-Jiangcuo fault (KPJF) and Maqin-Maqu segment, resulting in higher seismic risk in the future.

Abstract Background Monkeypox is an emerging infectious disease with confirmed cases and deaths in several parts of the world. In light of this crisis, this study aims to analyze the global knowledge pattern of monkeypox-related patents and explore current trends and future technical directions in the medical development of monkeypox to inform research and policy. Methods A comprehensive study of 1,791 monkeypox-related patents worldwide was conducted using the Derwent patent database by descriptive statistics, social network method and linear regression analysis. Results Since the 21st century, the number of monkeypox-related patents has increased rapidly, accompanied by increases in collaboration between commercial and academic patentees. Enterprises contributed the most in patent quantity, whereas the initial milestone patent was filed by academia. The core developments of technology related to the monkeypox include biological and chemical medicine. The innovations of vaccines and virus testing lack sufficient patent support in portfolios. Conclusions Monkeypox-related therapeutic innovation is geographically limited with strong international intellectual property right barriers though it has increased rapidly in recent years. The transparent licensing of patent knowledge is driven by the merger and acquisition model, and the venture capital, intellectual property and contract research organization model. Currently, the patent thicket phenomenon in the monkeypox field may slow the progress of efforts to combat monkeypox. Enterprises should pay more attention to the sharing of technical knowledge, make full use of drug repurposing strategies, and promote innovation of monkeypox-related technology in hotspots of antivirals (such as tecovirimat, cidofovir, brincidofovir), vaccines (JYNNEOS, ACAM2000), herbal medicine and gene therapy.

ABSTRACT: Periplaneta americana residue is a byproduct of using Periplaneta americana in pharmaceutical research and development for extracting active ingredients. Three hundred Three-yellow chickens were selected for the experiment and randomly divided into 6 groups (5 replications per group, 10 chickens per replicate): the control group (group A) was fed a basal ration, and the experimental groups (groups B, C, D, E, and F) were fed experimental diets in which P. americana residue replaced puffed soybean meal at proportions of 20, 40, 60, 80, and 100%, respectively, for a period of 42 d. The aim was to assess the impact of different levels of P. americana residue on the growth, survival, intestinal morphology, digestive enzyme activity, intestinal flora, and intestinal transcriptional responses of Three-yellow chickens. The results indicated that the increase in P. americana residue levels had a linear and quadratic impact on the average daily gain (ADG) and feed conversion ratio (FCR), respectively. The ADG was notably greater in the 40% group than in the 100% group, while the FCR was significantly lower in the 20% and 40% groups than in the 100% group (P < 0.05). Protease, lipase, and amylase activities exhibited a quadratic increase with increasing concentrations of P. americana residue (P < 0.05). Protease and lipase activities were notably greater in the 20% and 40% groups than in the 0% group (control group), amylase activity was significantly greater in the 40% group than in the 0% group (control group) (P < 0.05). Duodenal crypt depth (CD) decreased quadratically with increasing P. americana residue (P < 0.05). The duodenal villus height/crypt depth ratio (V/C) was significantly lower in the 100% group than in the 60% group (P < 0.05). The intestinal villus height (VH) increased quadratically with increasing levels of P. americana residue. The VH in the 60% group was significantly greater than that in the 0% (control group), 20, 80, and 100% groups (P < 0.05). The Chao and Ace indices demonstrated linear and quadratic increases with increasing levels of P. americana residue, while the Pd index showed a quadratic increase with increasing levels of P. americana residue (P < 0.05). The relative abundance profile of Lactobacillus exhibited a linear and quadratic decrease with increasing levels of P. americana residue, with the 100% group showing a significantly lower abundance than the 0% (control group) and 40% groups (P < 0.05). The transcriptome results showed that P. americana residue could enhance the digestive system by promoting vitamin, fat, carbohydrate digestion and absorption, cholesterol metabolism, etc. In conclusion, P. americana residue can replace puffed soybean meal without negatively affecting the growth performance of three-yellow chickens. The low and medium groups had positive effects on the growth performance, digestive enzyme activity, intestinal morphology, intestinal flora, and substance digestion and absorption of three-yellow chickens. The recommended replacement of P. americana residue for puffed soybean meal in the diets of three-yellow chickens ranged from 20% to 60%.

Carbon Capture, Storage and Utilization (CCS/CCU) is critical for achieving net-zero emissions. Although the recent surge in CCS/CCU projects announcement, there is a clear gap between announced capacity (around 400 Mt CO₂ per year) and the Net Zero Emissions (NZE) scenario deployment target (around 1 Gt per year) by 2030. This review examines breakthroughs and advancements across both established and emerging CCS/CCU systems with different Technology Readiness Levels (TRLs) in various industrial sectors, emphasizing the necessity of prospective assessments for their acceleration and scalability. It examines the development and application of prospective Life Cycle Assessment (pLCA) and prospective Techno-Economic Assessment (pTEA), highlighting their limitations and importance of their outcomes in decision-making processes. Differences between the evolving dynamics of the technological systems (foreground) and the evolution of the overall socioeconomic system (background) are discussed. Incorporating scenario data from Integrated Assessment Models (IAMs) into pLCA and pTEA reveals an iterative relationship that significantly influences the outcome of both the environmental assessments and the economics of large-scale production of the CCS/CCU systems under study. This, in turn, could reshape investment strategies towards advanced technologies, necessitating their consideration within the evolving structure of IAMs. It is concluded that the inherent limitations of CCS/CCU technologies at an early stage of development require quantitative uncertainty analysis and demand robustness, interdisciplinary collaboration, policy intervention, and data transparency. The rigorous evaluative frameworks are key for developing economic, environmental and climate policies and enable well-informed decisions across rapidly evolving sectors. A framework is proposed in this review, outlining a multistep process that includes a series of databases and open-source tools to interface pTEA and pLCA with enhanced IAMs for CCS/CCU, demonstrating its potential to improve decision-making and policy development.

IntroductionHepatitis E (HE), caused by the Hepatitis E virus (HEV), is a significant cause of acute viral hepatitis globally and a major public health concern, particularly in specific high-prevalence areas in China, which have diverse transmission routes and regional differences. Identifying the primary risk factors for HE transmission is essential to develop targeted interventions for vulnerable populations.MethodsThis study employed a 1:1 matched case–control methodology, using a standardized questionnaire complemented by medical records for data validation.ResultsAmong the 442 HE cases and 428 healthy controls, the case group had a higher prevalence of fatigue (46.21%) and loss of appetite (43.84%) compared to the control group. Furthermore, liver function indicators were significantly higher in the case group, with an average alanine aminotransferase (ALT) level of 621.94 U/L and aspartate aminotransferase (AST) level of 411.53 U/L. Severe HE patients were predominantly male, with significantly increased ALT and AST levels reaching 1443.81 U/L and 862.31 U/L respectively, along with a higher incidence of fatigue (90%) and loss of appetite (75%). Multifactorial analysis indicated that frequent dining out (OR = 2.553, 95%CI:1.686–3.868), poor hygiene conditions (OR = 3.889, 95%CI:1.399–10.807), and comorbid chronic illnesses (OR = 2.275, 95%CI:1.616–3.202) were risk factors for HE infection; conversely, good hygiene practices were protective factors against HE infection (OR = 0.698, 95%CI:0.521–0.934).ConclusionIn conclusion, HE infection in Zhejiang Province is closely associated with dietary habits and environmental hygiene, and individuals with chronic diseases or co-infections are at increased risk. This highlights the need for targeted health education to reduce the incidence of HE among these populations.

Abstract Protein methylation is a commonly posttranslational modification of transcriptional regulators to fine-tune protein function, however, whether this regulation strategy participates in the regulation of lignocellulase synthesis and secretion in Trichoderma reesei remains unexplored. Here, a putative protein methyltransferase (TrSAM) is screened from a T. reesei mutant with the ability to express heterologous β-glucosidase efficiently even under glucose repression. The deletion of its encoding gene trsam causes a significant increase of cellulase activities in all tested T. reesei strains, including transformants of expressing heterologous genes using cbh1 promotor. Further investigation confirms that TrSAM interacts with the cellulase negative regulator ACE1 via its amino acid residue Arg383, which causes a decrease in the ACE1-DNA binding affinity. The enzyme activity of a T. reesei strain harboring ACE1R383Q increases by 85.8%, whereas that of the strains with trsam or ace1 deletion increases by more than 100%. By contrast, the strain with ACE1R383K shows no difference to the parent strain. Taken together, our results demonstrate that TrSAM plays an important role in regulating the expression of cellulase and heterologous proteins initiated by cbh1 promotor through interacting with ACE1R383. Elimination and mutation of TrSAM and its downstream ACE1 alleviate the carbon catabolite repression (CCR) in expressing cellulase and heterologous protein in varying degrees. This provides a new solution for the exquisite modification of T. reesei chassis.

Abstract Taxol is a widely-applied anticancer drug that inhibits microtubule dynamics in actively replicating cells. Although a minimum 19-step biosynthetic pathway has been proposed and 16 enzymes likely involved have been characterized, stepwise biosynthetic reactions from the well-characterized di-oxygenated taxoids to Taxol tetracyclic core skeleton are yet to be elucidated. Here, we uncover the biosynthetic pathways for a few tri-oxygenated taxoids via confirming the critical reaction order of the second and third hydroxylation steps, unearth a taxoid 9α-hydroxylase catalyzing the fourth hydroxylation, and identify CYP725A55 catalyzing the oxetane ester formation via a cascade oxidation-concerted acyl rearrangement mechanism. After identifying a acetyltransferase catalyzing the formation of C7-OAc, the pathway producing the highly-oxygenated 1β-dehydroxybaccatin VI with the Taxol tetracyclic core skeleton is elucidated and its complete biosynthesis from taxa-4(20),11(12)-diene-5α-ol is achieved in an engineered yeast. These systematic studies lay the foundation for the complete elucidation of the biosynthetic pathway of Taxol.

Abstract Background A lack of force feedback in laparoscopic surgery often leads to a steep learning curve to the novices and traditional training system equipped with force feedback need a high educational cost. This study aimed to use a laparoscopic grasper providing force feedback in laparoscopic training which can assist in controlling of gripping forces and improve the learning processing of the novices. Methods Firstly, we conducted a pre-experiment to verify the role of force feedback in gripping operations and establish the safe gripping force threshold for the tasks. Following this, we proceeded with a four-week training program. Unlike the novices without feedback (Group A2), the novices receiving feedback (Group B2) underwent training that included force feedback. Finally, we completed a follow-up period without providing force feedback to assess the training effect under different conditions. Real-time force parameters were recorded and compared. Results In the pre-experiment, we set the gripping force threshold for the tasks based on the experienced surgeons’ performance. This is reasonable as the experienced surgeons have obtained adequate skill of handling grasper. The thresholds for task 1, 2, and 3 were set as 0.731 N, 1.203 N and 0.938 N, respectively. With force feedback, the gripping force applied by the novices with feedback (Group B1) was lower than that of the novices without feedback (Group A1) (p

PURPOSE: In patients undergoing endovascular thrombectomy (EVT) with acute ischemic stroke (AIS), dynamic cerebral autoregulation (dCA) may minimize neurological injury from blood pressure fluctuations. This study set out to investigate the function of dCA in predicting clinical outcomes following EVT. METHODS: 43 AIS of the middle cerebral or internal carotid artery patients underwent with EVT, and 43 healthy individuals (controls) were enrolled in this case control research. The dCA was evaluated using transcranial Doppler 12 h and five days after EVT. The transfer function analysis was used to derive the dCA parameters, such as phase, gain, and coherence. The modified Rankin scale (mRS) at 3 months after EVT was used to assess the clinical outcomes. Thefavorable outcome group was defined with mRS ≤2 and the unfavorable outcome group was defined with mRS score of 3–6. Logistic regression analysis was performed to determine the risk factors of clinical outcomes. RESULTS: A significant impairment in dCA was observed on the ipsilateral side after EVT, particularly in patients with unfavorable outcomes. After 5 days, the ipsilateral phase was associated with poor functional outcomes (adjusted odds ratio [OR] = 0.911, 95% confidence interval [CI]: 0.854–0.972; P = 0.005) and the area under the curve (AUC) (AUC, 0.878, [95% CI: 0.756–1.000] P < 0.001) (optimal cutoff, 35.0°). Phase change was an independent predictor of clinical outcomes from 12 h to 5 days after EVT (adjusted OR = 1.061, 95% CI: 1.016–1.109, P = 0.008). CONCLUSIONS: dCA is impaired in patients with AIS after EVT. Change in dCA could be an independent factor related to the clinical outcomes.

The vast majority of data obtained from sequence analysis of influenza A viruses (IAVs) have revealed that nonstructural 1 (NS1) proteins from H1N1 swine, H3N8 equine, H3N2 avian and the correspondent subtypes from dogs have a conserved four C-terminal amino acid motif when independent cross-species transmission occurs between these species. To test the influence of the C-terminal amino acid motifs of NS1 protein on the replication and virulence of IAVs, we systematically generated 7 recombinants, which carried naturally truncated NS1 proteins, and their last four C-terminal residues were replaced with PEQK and SEQK (for H1N1), EPEV and KPEI (for H3N8) and ESEV and ESEI (for H3N2) IAVs. Another recombinant was generated by removing the C-terminal residues by reverse genetics. Remarkably, the ESEI and KPEI motifs circulating in canines largely contributed efficient replication in cultured cells and these had enhanced virulence. In contrast, the avian ESEV motif was only responsible for high pathogenicity in mice. We examined the effects of these motifs upon interferon (IFN) induction. The 7 mutant viruses replicated in vitro in an IFN-independent manner, and the canine SEQK motif was able to induced higher levels of IFN-β in human cell lines. These findings shed further new light on the role of the four C-terminal residues in replication and virulence of IAVs and suggest that these motifs can modulate viral replication in a species-specific manner.

This study aimed to evaluate the genetic diversity and structure within the Dengchuan cattle population and effectively protect and utilize their germplasm resources. Herein, the single-nucleotide polymorphisms (SNPs) of 100 Dengchuan cattle (46 bulls and 54 cows) were determined using the GGP Bovine 100K SNP Beadchip. The results showed that among the Dengchuan cattle, a total of 101,220 SNPs were detected, and there were 83,534 SNPs that passed quality control, of which 85.7% were polymorphic. The average genetic distance based on identity-by-state (IBS) within the conservation population of Dengchuan cattle was 0.26 ± 0.02. A total of 3,999 genome-length runs of homozygosity (ROHs) were detected in the Dengchuan cattle, with ROH lengths primarily concentrated in the range of 1–5 Mb, accounting for 87.02% of the total. The average inbreeding coefficient based on ROHs was 4.6%, within the conservation population of Dengchuan cattle, whereas it was 4.9% for bulls, and the Wright inbreeding coefficient (FIS) value was 2.4%, demonstrating a low level of inbreeding within the Dengchuan cattle population. Based on neighbor-joining tree analysis, the Dengchuan cattle could be divided into 16 families. In summary, the conservation population of Dengchuan cattle displays relatively abundant diversity and a moderate genetic relationship. Inbreeding was observed among a few individuals, but the overall inbreeding level of the population remained low. It is important to maintain this low level of inbreeding when introducing purebred bloodlines to expand the core group. This approach will ensure the long-term conservation of Dengchuan cattle germplasm resources and prevent loss of genetic diversity.

Histamine is a biogenic amine with various physiological functions. However, excessive consumption of histamine can lead to various symptoms, and pose a threat to human lives. A ratiometric fluorescent test strip for visual detection of histamine was developed based on CB-Ni2+@CDs probes. As the concentration of histamine increases, the test strips exhibit a transition in fluorescence signal from yellow-green to blue. The RGB values were extracted from the images, and used for quantitative analysis of histamine. The method had a linear range of 0–1.0 mM, with a detection limit of 0.086 mM. The test strips were employed for the detection of histamine, and the recovery rate was found to be in the range of 88.3% to 104.69%, indicating a high level of accuracy. The uniqueness of the test strips lies in their ability to be produced simply by mixing CB, Ni2+ on a suitable polyvinyl alcohol/wood cellulose fiber substrate.

Abstract The impact of external factors on the human gut microbiota and how gut microbes contribute to human health is an intriguing question. Here, the gut microbiome of 3,224 individuals (496 with serum metabolome) with 109 variables is studied. Multiple analyses reveal that geographic factors explain the greatest variance of the gut microbiome and the similarity of individuals’ gut microbiome is negatively correlated with their geographic distance. Main food components are the most important factors that mediate the impact of host habitats on the gut microbiome. Diet and gut microbes collaboratively contribute to the variation of serum metabolites, and correlate to the increase or decrease of certain clinical indexes. Specifically, systolic blood pressure is lowered by vegetable oil through increasing the abundance of Blautia and reducing the serum level of 1‐palmitoyl‐2‐palmitoleoyl‐GPC (16:0/16:1), but it is reduced by fruit intake through increasing the serum level of Blautia improved threonate. Besides, aging‐related clinical indexes are also closely correlated with the variation of gut microbes and serum metabolites. In this study, the linkages of geographic locations, diet, the gut microbiome, serum metabolites, and physiological indexes in a Chinese population are characterized. It is proved again that gut microbes and their metabolites are important media for external factors to affect human health.

Persister cells are transiently tolerant to antibiotics and are associated with recalcitrant chronic infections due to recolonization of host cells after antibiotic removal. Brucella spp. are facultative pathogens that establish intracellular infection cycles in host cells which results in chronic persistent infections. Brucella abortus forms multi-drug persister cells which are promoted by the (p)ppGpp synthetase Rsh during rifampicin exposure. Here, we confirmed that Rsh promoted persister cells formation in B. abortus stationary phase treated with rifampicin and enrofloxacin. Deletion of the gene for Rsh decreased persister cells level in the presence of these drugs in different growth phases. However, persister cells formation by deletion strain varied in different growth phases in the presence of other antibiotics. Rsh also was involved in persister cells formation during rifampicin treatment under certain stress conditions, including acidic conditions, exposure to PBS, and heat stress. Moreover, Rsh impacted persister cell levels during rifampicin or enrofloxacin treatment in RAW264.7 macrophages. Certain typeIItoxin-antitoxin modules were upregulated under various stress conditions in B. abortus. We established that Rsh positively regulated the type II toxin-antitoxin mbcTA. Moreover, rifampicin-tolerant persister cells formation was elevated and ATP levels were decreased when mbcTA promoter was overexpressed in Rsh deletion background in stationary phase. Our results establish that (p)ppGpp synthetase Rsh plays a key role in B. abortus persistence and may serve as a potent novel target in combination with rifampicin in the development of new therapeutic approaches and prevention strategies to treat chronic infections of Brucella.

Essential oils have been recognized for their strong antibacterial property, making them an innovative approach for preserving meat. However, their chemical instability and direct impact on meat proteins limit their application. To overcome these limitations, various loading systems have been explored. This study aimed to compare the effect of cinnamon essential oil (CEO) loaded in a liposome and emulsion system on the proteolysis of minced pork and to evaluate the advantages of each delivery system in preventing microorganism-induced quality deterioration of meat. Minced pork treated with CEO-liposomes exhibited lower pH, total volatile basic nitrogen (TVB-N), and total viable count (TVC) values than CEO-emulsions and provided better protection against microorganisms. SDS-polyacrylamide gel electrophoresis (PAGE) analysis confirmed that CEO-liposome was more effective in protecting proteins from degradation. Moreover, CEO-liposome produced lower amount of bitter amino acids and harmful biogenic amines. Antibacterial mechanisms indicated that CEO-liposome exhibited a stronger inhibitory effect against major spoilage bacteria in meat products by increasing cell membrane permeability. The membrane damage was further supported by an increase in conductivity and the leakage of nucleic acids. Compared to the CEO-emulsion system, CEO-liposome emerged as an effective preservative for minced pork. These results provided important theoretical support for using a bioactive compound delivery system to prevent microorganism-induced quality deterioration in meat.

Objective: To establish a Bama minipigs model with Non-Alcoholic Fatty Liver (NAFL) induced by a high-fat diet and investigate the application of attenuation coefficient (ATT) and ultrasound-derived fat fraction (UDFF) in the diagnosis of NAFL. Methods: Six-month-old male Bama minipigs were randomly divided into normal control and high-fat groups (n = 3 pigs per group), and fed with a control diet and high-fat diet for 32 weeks. Weight and body length were measured every four weeks, followed by quantitative ultrasound imaging (ATT and UDFF), blood biochemical markers, and liver biopsies on the same day. Using the Non-Alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) as a reference, we analyzed the correlation between ATT, UDFF, and their score results. Results: Compared with the normal control group, the body weight, body mass index (BMI), and serum levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in the High-fat group were significantly different at Week 12 (P

While diagnosing multiple lesion regions in chest X-ray (CXR) images, radiologists usually apply pathological relationships in medicine before making decisions. Therefore, a comprehensive analysis of labeling relationships in different data modes is essential to improve the recognition performance of the model. However, most automated CXR diagnostic methods that consider pathological relationships treat different data modalities as independent learning objects, ignoring the alignment of pathological relationships among different data modalities. In addition, some methods that use undirected graphs to model pathological relationships ignore the directed information, making it difficult to model all pathological relationships accurately. In this paper, we propose a novel multi-label CXR classification model called MRChexNet that consists of three modules: a representation learning module (RLM), a multi-modal bridge module (MBM) and a pathology graph learning module (PGL). RLM captures specific pathological features at the image level. MBM performs cross-modal alignment of pathology relationships in different data modalities. PGL models directed relationships between disease occurrences as directed graphs. Finally, the designed graph learning block in PGL performs the integrated learning of pathology relationships in different data modalities. We evaluated MRChexNet on two large-scale CXR datasets (ChestX-Ray14 and CheXpert) and achieved state-of-the-art performance. The mean area under the curve (AUC) scores for the 14 pathologies were 0.8503 (ChestX-Ray14) and 0.8649 (CheXpert). MRChexNet effectively aligns pathology relationships in different modalities and learns more detailed correlations between pathologies. It demonstrates high accuracy and generalization compared to competing approaches. MRChexNet can contribute to thoracic disease recognition in CXR.

ABSTRACTAfter harvest, paddy rice may encounter frozen conditions during the storage and transportation periods. However, the effect of frozen storage on quality of paddy rice remains unclear. In this research, two moisture contents of paddy rice (13.5% and 15.1%) were stored at two frozen temperatures (−18°C and −30°C) for two months and then evaluated for quality attributes, including germination rate, peroxidase and polyphenol oxidase activities, fat acidity, milling quality, pasting property, cooking property, and texture of the cooked rice. The results showed that the frozen storage generally decreased the germination rate, activities of peroxidase and polyphenol oxidase, husked rice yield, head rice yield of paddy rice, reduced the water uptake ratio and volume expansion rate of milled rice during cooking, and lowered the hardness of cooked rice. At frozen condition, the decrease of temperature and the increase of moisture content led to a more pronounced reduction in germination rate and peroxidase activity. Frozen treatment of paddy rice did not significantly affect the pasting temperature of milled rice flour, but decreased the peak viscosity. Fat acidity of paddy rice slightly increased after frozen storage.

Our aim was to explore the aberrant intrinsic functional topology in methamphetamine-dependent individuals after six months of abstinence using resting-state functional magnetic imaging (rs-fMRI). Eleven methamphetamines (MA) abstainers who have abstained for six months and eleven healthy controls (HC) were recruited for rs-fMRI examination. The graph theory and functional connectivity (FC) analysis were employed to investigate the aberrant intrinsic functional brain topology between the two groups at multiple levels. Compared with the HC group, the characteristic shortest path length ($ {L}_{p} $) showed a significant decrease at the global level, while the global efficiency ($ {E}_{glob} $) and local efficiency ($ {E}_{loc} $) showed an increase considerably. After FDR correction, we found significant group differences in nodal degree and nodal efficiency at the regional level in the ventral attentional network (VAN), dorsal attentional network (DAN), somatosensory network (SMN), visual network (VN) and default mode network (DMN). In addition, the NBS method presented the aberrations in edge-based FC, including frontoparietal network (FPN), subcortical network (SCN), VAN, DAN, SMN, VN and DMN. Moreover, the FC of large-scale functional brain networks revealed a decrease within the VN and SCN and between the networks. These findings suggest that some functions, e.g., visual processing skills, object recognition and memory, may not fully recover after six months of withdrawal. This leads to the possibility of relapse behavior when confronted with MA-related cues, which may contribute to explaining the relapse mechanism. We also provide an imaging basis for revealing the neural mechanism of MA-dependency after six months of abstinence.

Circulating tumor cells (CTCs) that undergo epithelial-to-mesenchymal transition (EMT) can provide valuable information regarding metastasis and potential therapies. However, current studies on the EMT overlook alternative splicing. Here, we used single-cell full-length transcriptome data and mRNA sequencing of CTCs to identify stage-specific alternative splicing of partial EMT and mesenchymal states during pancreatic cancer metastasis. We classified definitive tumor and normal epithelial cells via genetic aberrations and demonstrated dynamic changes in the epithelial-mesenchymal continuum in both epithelial cancer cells and CTCs. We provide the landscape of alternative splicing in CTCs at different stages of EMT, uncovering cell-type-specific splicing patterns and splicing events in cell surface proteins suitable for therapies. We show that MBNL1 governs cell fate through alternative splicing independently of changes in gene expression and affects the splicing pattern during EMT. We found a high frequency of events that contained multiple premature termination codons and were enriched with C and G nucleotides in close proximity, which influence the likelihood of stop codon readthrough and expand the range of potential therapeutic targets. Our study provides insights into the EMT transcriptome’s dynamic changes and identifies potential diagnostic and therapeutic targets in pancreatic cancer.

The planting area of high-quality indica rice varieties has been growing rapidly in China. However, the storage characteristics of these varieties remains unclear. In this research, different moisture contents (13.5, 14.5, and 15.5%) of high-quality rice (variety Xiadao No.1) were stored at different temperatures (15, 20, 25, and 30°C) for 360 d, and then evaluated for lipid metabolism, redox enzyme activities, fatty acid composition, and sensory attributes. With the prolongation of storage, rice displayed an upward trend in fatty acid value, malondialdehyde content, and cooked rice hardness and a downward trend in contents of total fat and non-starch lipid, peroxidase and catalase activities, and sensory score of cooked rice. The change trends of these quality parameters were aggravated by elevating storage temperature and moisture content. Linoleic acid content of rice generally decreased with prolonged storage. After 300 d of storage, rice with initial moisture content of 13.5% at 30°C showed a fatty acid value of higher than 30 mg KOH/100 g, while rice of other two initial moisture contents reached similar level at 25°C. After the whole storage period, only rice with initial moisture contents of 13.5 and 14.5% stored at 15°C had a sensory score of higher than 60. These results suggested that the aging process of high-quality rice can be inhibited by decreasing the storage temperature and initial moisture content. These results can provide reference for grain storage enterprises to select proper storage condition to store high-quality rice.

Summary: Liver injury stimulates hepatocyte replication and hepatic stellate cell (HSC) activation, thereby driving liver regeneration. Aberrant HSC activation induces liver fibrosis. However, mechanisms underlying liver regeneration and fibrosis remain poorly understood. Here, we identify hepatic Snai1 and Snai2 as important transcriptional regulators for liver regeneration and fibrosis. Partial hepatectomy or CCl4 treatment increases occupancies of Snai1 and Snai2 on cyclin A2 and D1 promoters in the liver. Snai1 and Snai2 in turn increase promoter H3K27 acetylation and cyclin A2/D1 expressions. Hepatocyte-specific deletion of both Snai1 and Snai2, but not one alone, suppresses liver cyclin A2/D1 expression and regenerative hepatocyte proliferation after hepatectomy or CCl4 treatments but augments CCl4-stimulated HSC activation and liver fibrosis. Conversely, Snai2 overexpression in the liver enhances hepatocyte replication and suppresses liver fibrosis after CCl4 treatment. These results suggest that hepatic Snai1 and Snai2 directly promote, via histone modifications, reparative hepatocyte replication and indirectly inhibit liver fibrosis.

ObjectiveThis study was designed to investigate the prevalence of religious belief and its relationship with psychiatric symptoms among Chinese adolescents.MethodsThis study recruited 11,603 adolescents in Grades 7-9 from March 21 to 31, 2020 in five cities in China. The religious beliefs of adolescents were collected by asking whether they held religious beliefs and what type of religious beliefs they held. The Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 Scale (GAD-7) were used to assess depressive and anxiety symptoms in all adolescents. Demographics, religious beliefs, and mental health status were collected through the professional version of Wenjuanxing.ResultsOf 11,069 valid questionnaires collected, 847 (7.7%) reported holding religious beliefs. Adolescents with religious beliefs showed significantly more severe symptoms of depression and anxiety compared to those without religious beliefs (both p

The prevalence of cadmium (Cd) contamination has emerged as a significant global concern. Exposure to Cd during pregnancy is associated with adverse pregnancy outcomes, including miscarriage. However, there is currently a lack of comprehensive summaries on Cd-induced miscarriage. Therefore, it is imperative to further strengthen research into in vivo studies, clinical status, pathological mechanisms, and pharmacological interventions for Cd-induced miscarriage. This study systematically presents the current knowledge on animal models and clinical trials investigating Cd exposure-induced miscarriage. The underlying mechanisms involving oxidative stress, inflammation, endocrine disruption, and placental dysfunction caused by Cd-induced miscarriage are also extensively discussed. Additionally, potential drug interventions such as melatonin, vitamin C, and vitamin E are highlighted for their pharmacological role in mitigating adverse pregnancy outcomes induced by Cd.

In this study, amine vapor-sensitive films with ratiometric fluorescence attributes were developed. The pH-sensitive fluorescein 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) and its tetraphenylethylene derivative (TPB) were selected as ratiometric indicators and incorporated into a polyvinyl alcohol (PVA) matrix to produce HPTS/TPB-PVA films. The films responded well to amine vapors, and the interference of aromatic vapors did not substantially affect the fluorescence signals of the films. Under UV light at a wavelength of 365 nm, the fluorescence of the films changed from dark pink to light pink and finally to yellow when the freshness of the fish was visually checked during storage. In addition, the color difference values of the films showed a positive correlation with the total volatile basic nitrogen (TVB-N), ranging from 12.7 to 24.8 mg/100 g at 25 °C and 8.4 to 25.6 mg/100 g at 4 °C, respectively. This indicates that fluorescent films have good potential for quantifying fish freshness in the near future when connected to an automatic data processing system based on color differences.

Abstract Colorectal cancer (CRC) is a complex malignancy, influenced not only by cancer cells but also by the tumor microenvironment (TME). Within the TME, emerging evidence highlights the presence and functional roles of diverse microbial entities, referred to as intratumoral microbiota. The distribution of these microbiota exhibits significant heterogeneity and engages in dynamic interactions with tumor cells, forming a unique ecosystem. Certain bacterial strains distinctly influence the TME of CRC, affecting the characteristics and progression of the tumor. This review summarizes the intricate roles of intratumoral microbiota within CRC's TME, emphasizing their importance in the disease's development and progression, and discuss the opportunities and challenges in the field.

In actual storage processes of rice, environment temperatures fluctuate rather than remain constant. Accumulated temperature is the sum of temperature during the storage period. In this research, six different temperature-varied conditions with two accumulated temperatures (low intensity: 7200°C⸱d; high intensity: 9000°C⸱d) were designed to store rice for 12 months and the stored rice samples were compared in quality. Three low-accumulated temperature conditions were set as follows: No. 4–15°C for 6 months followed by 25°C; No. 5–25°C for 6 months followed by 15°C; No. 8-alternating between 15°C and 25°C every 2 months. Similarly, three high-intensity conditions, No. 6, No. 7, and No. 9, were set with a temperature change from 25°C to 35°C. Three constant temperature conditions, No. 1, No. 2, and No. 3, with storage temperature of 15, 25, and 35°C, respectively, were used as controls. Under temperature-varied conditions, rice demonstrated a decline in germination rate (GR), catalase (CAT) and peroxidase (POD) activities, and an increase in fatty acid value (FAV) as storage time increased. After storage, rice exhibited higher water absorption rate (WAR) and volume expansion rate (VER), but reduced stickiness and sensory scores for appearance, taste and overall quality. Generally, three batches at high-accumulated temperature conditions had lower GR and sensory scores, and higher FAV, WAR, and VER compared to those under low-intensity conditions. Furthermore, variations in the sequence of temperature also affected quality parameters, even at the same accumulated temperature. These findings indicate that under temperature-varied conditions, increased accumulated temperature exacerbates rice deterioration, and different temperature sequences can influence quality at a given accumulated temperature.

Abstract High frequency (HF)-rTMS has been shown to improve cognitive functions in patients with schizophrenia (SCZ). This study aimed to investigate whether COX-2 rs5275 variants were associated with cognitive improvements following rTMS treatment in patients with SCZ. Forty-eight hospitalized patients with SCZ were assigned to the neuronavigation HF-rTMS group and 28 patients to the sham group over left DLPFC for 1 month. Cognitive function was evaluated using the repeatable battery for the assessment of neuropsychological status (RBANS) at weeks 0 and 4. COX-2 rs5275 polymorphism was genotyped by a technician. At baseline, C allele carriers showed better cognitive performance relative to patients with TT homozygote. Additionally, C allele carriers had greater improvement in memory from the follow-up to baseline following rTMS stimulation, while patients with the TT genotype showed no significant improvement in memory index. More importantly, we found that COX-2 rs5275 was correlated with the response to rTMS after controlling for the covariates. This study data indicate that COX-2 rs5275 was associated with improvements in immediate memory after HF-rTMS treatment in patients with SCZ. rTMS shows an effect on memory only in C allele carriers, but not in those with the TT genotype.

ABSTRACTGrain sprouting poses a significant global challenge, especially for wheat. Nonetheless, recent investigators have unveiled numerous benefits of germination. In this study, we incorporated various proportions of sprouted wheat flour (SF) into wheat flour to produce sprouted wheat steamed bread (SWSB). The impact of SF on the quality of flour and SWSB was evaluated, resulting a development of GABA-enhanced, green-healthy SWSB. With increased addition of SF, the falling number, pasting viscosity, and dough stability time of flour exhibited significant decreases, whereas the gluten index initially increased and then decreased. The textural properties, such as hardness, chewiness, adhesion, springiness, and cohesion, exhibited varying degrees of fluctuation with increasing SF levels. The specific volume of SWSB was optimal at an SF concentration of 6% and the sensory score was highest at 2%. Lightness of SWSB was comparable to that of the control at 4% SF addition. C-cell images revealed that the fineness of the SWSB texture initially increased and then decreased with increasing SF levels. Overall, an SF concentration of 4% was found to be optimal for dough properties, color, texture characteristics and sensory quality, providing a theoretical foundation for industrial production and application.

Tumor-infiltrating T cells are essential players in tumor immunotherapy. Great progress has been achieved in the investigation of T cell heterogeneity. However, little is well known about the shared characteristics of tumor-infiltrating T cells across cancers. In this study, we conduct a pan-cancer analysis of 349,799 T cells across 15 cancers. The results show that the same T cell types had similar expression patterns regulated by specific transcription factor (TF) regulons across cancers. Multiple T cell type transition paths were consistent in cancers. We found that TF regulons associated with CD8+ T cells transitioned to terminally differentiated effector memory (Temra) or exhausted (Tex) states were associated with patient clinical classification. We also observed universal activated cell-cell interaction pathways of tumor-infiltrating T cells in all cancers, some of which specifically mediated crosstalk in certain cell types. Moreover, consistent characteristics of TCRs in the aspect of variable and joining region genes were found across cancers. Overall, our study reveals common features of tumor-infiltrating T cells in different cancers and suggests future avenues for rational, targeted immunotherapies.

Abstract Probabilistic predictions for regression problems are more popular than point predictions and interval predictions, since they contain more information for test labels. Conformal predictive system is a recently proposed non-parametric method to do reliable probabilistic predictions, which is computationally inefficient due to its learning process. To build faster conformal predictive system and make full use of training data, this paper proposes the predictive system based on locally weighted jackknife prediction approach. The theoretical property of our proposed method is proved with some regularity assumptions in the asymptotic setting, which extends our earlier theoretical researches from interval predictions to probabilistic predictions. In the experimental section, our method is implemented based on our theoretical analysis and its comparison with other predictive systems is conducted using 20 public data sets. The continuous ranked probability scores of the predictive distributions and the performance of the derived prediction intervals are compared. The better performance of our proposed method is confirmed with Wilcoxon tests. The experimental results demonstrate that the predictive system we proposed is not only empirically valid, but also provides more information than the other comparison predictive systems.

BackgroundMycoplasma pneumoniae pneumonia (MPP) is common among children, but the impact of atopy on MPP severity in children is unknown. This study investigated whether atopic vs. nonatopic children had greater MPP severity.MethodsRetrospective analysis was conducted on 539 (ages 3–14 years) patients who were hospitalized in the First Affiliated Hospital of Anhui Medical University for MPP between January 2018 and December 2021, 195 were atopic and 344 were nonatopic. Of them, 204 had refractory MPP, and 335 had general MPP. And of atopic children, 94 had refractory MPP, and 101 had general MPP. Data on demographic and clinical characteristics, laboratory findings, clinical treatments were analyzed.ResultsSignificantly more boys with MPP were atopic than nonatopic (P

In comparison to orthogonal frequency division multiplexing (OFDM), the OFDM linear frequency modulation (OFDM-LFM) signal has similar time-bandwidth product, lower peak-to-average power ratio, and higher sensitivity to Doppler frequency shift, making it a promising candidate waveform for multiple-in multiple-out (MIMO) radar applications. However, the OFDM-LFM signal is unsatisfactory in practical applications due to the challenges in waveform design and its non-stationary property, which significantly degrades the performance of current high-resolution subspace techniques for direction of departure (DoD) and direction of arrival (DoA) angle estimation. In this paper, we first proposed a novel OFDM-LFM waveform design method based on the scale discrete Fresnel transform (SDFnT), which efficiently generates orthogonal LFM signals with unlimited number of subcarriers and can be convieniently implemented using the fast Fourier transform (FFT). Then, for angle estimation in OFDM-LFM MIMO radars, we presented a new scale discrete Fresnel transform multiple signal classification (SDFnT-MUSIC) method. By converting the steering vector into the chirp domain and making it non-time-vary, high resolution angle estimation for OFDM-LFM wideband signals can be achieved. Simulation results shows that the proposed waveform design method requires less computational time than conventional method based based on the fractional Fourier transform (FrFT), whereas the proposed DoA-DoD estimation method outperform the FrFT-MUSIC method in terms of computational complexity and target angle estimate performance.

Abstract Recently, the interest in extracellular vesicles released by bacteria has rapidly increased. Bacterial extracellular vesicles (BEVs) have been involved in bacteria‐bacteria and bacteria‐host interactions, which strengthen health or bring about various pathologies. However, BEV separation, characterization, and functional studies require the establishment of guidelines and further optimization in order to stimulate the development of science in BEV research and a following successful transformation into clinical applications. This position paper is authored by the Microbial Vesicles Task Force of the Chinese Society for Extracellular Vesicles (CSEV) composed of experienced medical laboratory specialists, microbiologists, virologists, biologists and material biologists who are actively engaged in BEV research. Herein, we present a concise description of BEV research and discover challenges and critical gaps in current BEV‐based analyses for clinical applications. Finally, we also offer suggestions and considerations to improve experimental reproducibility and interoperability in BEV research to promote progress in the field.

Abstract Background To evaluate the effectiveness of enhanced check to the duration of the central venous catheters associated bloodstream infections (CABSIs), and the impact on infection rates. Methods A before-after, real-world study in six adult intensive care units was conducted. All adult patients who had only one central venous catheter were included during two consecutive periods. The intervention period, added cross-check that all patients with central venous catheter (CVC) need to be performed, and included nurses' checks for insertion practices and doctors' checks for maintenance practices. Propensity scores matching were used to account for potential confounding, and restricted cubic spline was served as visualizing the CABSI risk. Results A total of 2906 patients with 26,157 CVC-days were analyzed. After intervention, the density incidence of CABSI decreased from 10.24 to 6.33/1,000 CVC-days (P

Zea mays (maize) is an important agricultural crop that produces a variety of valuable terpenoids, including several triterpenoids. However, no oxidosqualene cyclase (OSC) enzymes, which catalyze the first step in triterpenoid biosynthesis, have been identified in maize. Here, we identified a novel OSC (ZmOSC1) in maize using a combination of genomic mining and phylogenetic analyses. To functionally characterize the candidate OSC, we constructed a yeast strain that produced high levels of 2,3-oxidosqualene. When ZmOSC1 was expressed in this strain, three compounds were detected and identified as hop-17(21)-en-3-ol, hopenol B and simiarenol, respectively. For their biosynthesis, we proposed a potential cyclization mechanism catalyzed by ZmOSC1 via the generation of a dammarenyl cation, followed by sequential cationic ring expansion, cyclization, cationic migration and further proton elimination. This study discovered and characterized an OSC from maize for the first time, and laid a foundation to produce three bioactive pentacyclic triterpenes, hop-17(21)-en-3-ol, hopenol B and simiarenol, using synthetic biology approaches.

ObjectivesThis paper aims to address the numerical simulation problems of the dynamic response of ships subject to near-, medium- and far-field underwater explosions by establishing several numerical methods and calculation models. MethodsFirst, load and fluid-structure interaction models are established on the basis of the Eulerian finite element method and acoustic finite element method using the field-split technique, and FSLAB fluid-structure interaction software is developed. Next, near-, medium- and far-field underwater explosions are numerically simulated respectively. The shock wave propagation law, bubble shape and load evolution characteristics of near free-surface and near-wall underwater explosions are obtained, and the shock response characteristics of a spherical shell and ship subject to far-field underwater explosions are analyzed. Finally, the FSLAB software results are compared with the analytical solutions, reference solutions and experimental data. ResultsThe results show that the FSLAB fluid-structure interaction software developed in this paper is effective and accurate in simulating the impact damage of underwater explosions on warships. ConclusionThis study can provide a basis and support for the power assessment of underwater anti-explosion and shock design of warships.

In order to explore the relationship between storage conditions and the quality changes of high-quality indica rice, the high-quality indica rice “Fengyou 22” samples were stored at 4 storage temperatures (15, 20, 25 and 30 ℃) and 3 moisture contents (13.5%, 14.5% and 15.5%) and 2 gas composition (modified atmosphere with nitrogen, non-modified atmosphere) simulated storage for 360 d, and the yellow rice content, germination rate, electrical conductivity, α-amylase activity, fatty acid value, gel consistency, straight chain starch content, rice soup solids, iodine blue value and rice hardness, rice viscosity, rice balance, rice elasticity, appearance score, taste score, comprehensive score and other indicators were regularly determined. The results showed that the higher the storage temperature and the higher the moisture content, the more obvious the quality changed; under the same condition of storage temperature and moisture content, nitrogen storage had the effect of delaying the quality change. The principal component analysis method was used to analyze the 16 indicators, and 5 principal component factors with a cumulative contribution rate of 81.055% were obtained through dimensionality reduction. Representative quality indicators were chosen from the indicators with larger positive eigenvalues in each principal component, which were germination rate, electrical conductivity, iodine blue value and amylose content. The correlation analysis of the four characteristic indexes with storage temperature, moisture content and gas composition showed that storage temperature had the greatest influence on the characteristic indexes of high-quality indica rice, followed by moisture content then gas composition.

Abstract Background Enterovirus A (EV-A), such as enterovirus A71 (EV-A71), generally causes hand, foot, and mouth disease (HFMD). However, limited studies focused on uncommon enterovirus serotypes such as coxsackievirus A12 (CV-A12). This study aimed to provide evidence to determine the molecular characteristics of a CV-A12 strain isolated in Zhejiang province, China. Methods In routine surveillance of HFMD, we identified a child case with CV-A12 infection in 2019 in Zhejiang province, China. Enterovirus was examined by using real-time reverse transcription-PCR (qRT-PCR). A partial VP1 sequence was amplified to determine the serotype, and then a full-length CV-A12 genome was sequenced. Nucleotide and amino acid similarity was calculated with those CV-A12 strains available in GenBank. Recombination was detected using RDP 4 and SimPlot. Furthermore, phylogenetic analysis was conducted by using BEAST 1.10, and protein modeling was performed with I-TASSER webserver. Results A full-length CV-A12 genome PJ201984 was isolated in a Chinese child with HFMD. The similarities with complete coding sequences of the CV-A12 strains in GenBank ranged between 79.3–100% (nucleotide) and 94.4–100% (amino acid), whereas it was 88.7–100.0% (nucleotide) and 97.2–100% (amino acid) when excluding the CV-A12 prototype strain Texas-12. In PJ201984, amino acid variations were more divergent in P2 and P3 regions than those in P1; the majority of those variations in VP1 (13/15) and VP4 (7/8) were similar to those documented in recently isolated CV-A12 strains in China. Furthermore, recombination was identified in P2 region, which involved a CV-A5 strain collected in China. Phylogenetic analysis revealed that PJ201984 clustered together with multiple CV-A12 strains isolated in China and the Netherlands during 2013–2018, as compared to another cluster consisting of CV-A12 strains in China and France during 2009–2015. Additionally, protein models of VP1 and VP4 in PJ201984 were well predicted to be similar to VP1 protein of EV-A71 and VP4 protein of coxsackievirus A21, respectively. Conclusions The full-length CV-A12 genome was characterized to have common recombination in P2 region and be phylogenetically related to those CV-A12 strains isolated in recent years, suggesting a continual spread in China. It warrants strengthening the routine surveillance for uncommon enterovirus serotypes, particularly on possible recombination and variation.

A key missing enzyme in the plant Panax ginseng Rg2 and Re2 ginsenoside biosynthesis pathway is identified, and its expression is engineered in yeast for high-level production.