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Abstract Background Medical informed consent stands as an ethical and legal requisite preceding any medical intervention. Hospitalized patients face functional health literacy (FHL) challenges when dealing with informed consent forms (ICFs). The legitimacy of ICFs and informed consent procedures in China remains substantially undisclosed. The study’s aim was to investigate if Chinese patients have adequate FHL to be truly informed before providing medical consent. Methods In this cross-sectional, structured interview-based study, FHL was assessed within the context of the informed consent scenarios in two teaching hospitals (a 1500-bed general tertiary hospital and a 700-bed cancer hospital) affiliated with Shantou University Medical College. Twenty-seven patients admitted across clinical departments, along with their relatives (n = 59), were enrolled in the study after obtaining informed consent. The participants underwent a three-step assessment with two selected ICFs —teach-back skills, perceived understanding (perception), and informed knowledge (cognizance), with each component carrying a maximum score of 10. Data were analyzed with SPSS (version 22.0) for descriptive and inferential statistics, with consideration of significant P values as

Abstract Background and objectives Congenital heart defect (CHD) is one of the most common birth defects. The aim of this cohort study was to evaluate the prevalence of chromosomal abnormalities and the clinical utility of chromosomal microarray analysis (CMA) in fetuses with different types of CHD, aiming to assist genetic counseling and clinical decision-making. Methods In this study, 642 fetuses with CHD were enrolled from a single center over a six-year period (2017–2022). Both conventional karyotyping and CMA were performed simultaneously on these fetuses. Results The diagnostic yield of CMA in fetuses with CHD in our study was 15.3% (98/642). Our findings revealed a significant increase in the diagnostic yield of CMA compared to karyotyping in fetuses with CHD. Among CHD subgroups, the diagnostic yields were high in complex CHD (34.9%), conotruncal defects (28.6%), right ventricular outflow tract obstructive defects (RVOTO) (25.9%), atrioventricular septal defects (AVSD) (25.0%) and left ventricular outflow tract obstructive defects (LVOTO) (24.1%), while those in other CHD (10.6%) and septal defects (10.9%) were relatively low. The overall detection rate of clinically significant chromosomal abnormalities was significantly higher in the non-isolated CHD group compared to the isolated CHD group (33.1% vs. 9.9%, P

Abstract Cuproptosis is a newly identified form of cell death induced by excessive copper (Cu) accumulation within cells. Mechanistically, cuproptosis results from Cu-induced aggregation of dihydrolipoamide S-acetyltransferase, correlated with the mitochondrial tricarboxylic acid cycle and the loss of iron–sulfur cluster proteins, ultimately resulting in proteotoxic stress and triggering cell death. Recently, cuproptosis has garnered significant interest in tumor research due to its potential as a crucial therapeutic strategy against cancer. In this review, we summarized the cellular and molecular mechanisms of cuproptosis and its relationship with other types of cell death. Additionally, we reviewed the current drugs or strategies available to induce cuproptosis in tumor cells, including Cu ionophores, small compounds, and nanomedicine. Furthermore, we targeted cell metabolism and specific regulatory genes in cancer therapy to enhance tumor sensitivity to cuproptosis. Finally, we discussed the feasibility of targeting cuproptosis to overcome tumor chemotherapy and immunotherapy resistance and suggested future research directions. This study suggested that targeting cuproptosis could open new avenues for developing tumor therapy.

Abstract Helicobacter pylori (H. pylori), together with its CagA, has been implicated in causing DNA damage, cell cycle arrest, apoptosis, and the development of gastric cancer. Although lncRNA H19 is abundantly expressed in gastric cancer and functions as a pro-oncogene, it remains unclear whether lncRNA H19 contributes to the oncogenic process of H. pylori CagA. This study investigates the role of H19 in the DNA damage response and malignancy induced by H. pylori. It was observed that cells infected with CagA+ H. pylori strain (GZ7/cagA) showed significantly higher H19 expression, resulting in increased γH2A.X and p-ATM expression and decreased p53 and Rad51 expression. Faster cell migration and invasion was also observed, which was reversed by H19 knockdown in H. pylori. YWHAZ was identified as an H19 target protein, and its expression was increased in H19 knockdown cells. GZ7/cagA infection responded to the increased YWHAZ expression induced by H19 knockdown. In addition, H19 knockdown stimulated cells to enter the G2-phase and attenuated the effect of GZ7/cagA infection on the cellular S-phase barrier. The results suggest that H. pylori CagA can upregulate H19 expression, participate in the DNA damage response and promote cell migration and invasion, and possibly affect cell cycle arrest via regulation of YWHAZ.

Abstract Increasing evidence suggests an association between exercise duration and Parkinson’s disease. However, no high-quality prospective evidence exists confirming whether differences exist between the two modes of exercise, weekend warrior and equal distribution of exercise duration, and Parkinson’s risk. Hence, this study aimed to explore the association between different exercise patterns and Parkinson’s risk using exercise data from the UK Biobank. The study analyzed data from 89,400 UK Biobank participants without Parkinson’s disease. Exercise data were collected using the Axivity AX3 wrist-worn triaxial accelerometer. Participants were categorized into three groups: inactive, regularly active, and engaged in the weekend warrior (WW) pattern. The relationship between these exercise patterns and Parkinson’s risk was assessed using a multifactorial Cox model. During a mean follow-up of 12.32 years, 329 individuals developed Parkinson’s disease. In a multifactorial Cox model, using the World Health Organization–recommended threshold of 150 min of moderate-to-vigorous physical activity per week, both the active WW group [hazard ratio (HR) = 0.58; 95% confidence interval (CI) = 0.43–0.78; P

Abstract Introduction Stroke is a life-threatening condition that causes a major medical burden globally. The currently used methods for the prevention or prediction of stroke have certain limitations. Exposure to tobacco in early life, including smoking during adolescence and maternal smoking during pregnancy, can affect adolescent development and lead to several negative outcomes. However, the association between early-life tobacco exposure and stroke is not known. Methods In this prospective cohort study, for the analyses involving exposure to maternal smoking during pregnancy and age of smoking initiation, we included 304,984 and 342,893 participants, respectively., respectively from the UK Biobank. Cox proportional hazard regression model and subgroup analyses were performed to investigate the association between early-life tobacco exposure and stroke. Mediation analyses were performed to identify the mediating role of biological aging in the association between early tobacco exposure and stroke. Results Compared with participants whose mothers did not smoke during pregnancy, participants whose mothers smoked during pregnancy showed an 11% increased risk of stroke (HR: 1.11, 95% CI: 1.05–1.18, P

ABSTRACT Soil salinization usually occurs in arid and semi-arid climate areas from 37 to 50 degrees north latitude and 73 to 123 degrees east longitude. These regions are inhabited by a large number of Coleopteran insects, which play an important role in the ecological cycle. However, little is known about the endosymbiotic microbial taxa and their biological characteristics in these insects. A study of endosymbiotic microorganisms of Coleoptera from Xinjiang, a typical arid and inland saline area, revealed that endosymbiont bacteria with salinity tolerance are common among the endosymbionts of Coleoptera. Functional prediction of the microbiota analysis indicated a higher abundance of inorganic ion transporters and metabolism in these endosymbiont strains. Screening was conducted on the tolerable 11% NaCl levels of Brevibacterium casei G20 (PRJNA754761), and differential metabolite and proteins were performed. The differential metabolites of the strain during the exponential and plateau phases were found to include benzene compounds, organic acids, and their derivatives. These results suggest that the endosymbiotic microorganisms of Coleoptera in this environment have adaptive evolution to extreme environments, and this group of microorganisms is also one of the important resources for mining saline and alkaline-tolerant chassis microorganisms and high-robustness enzymes.IMPORTANCEColeoptera insects, as the first largest order of insect class, have the characteristics of a wide variety and wide distribution. The arid and semi-arid climate makes it more adaptable. By studying the endosymbiont bacteria of Coleoptera insects, we can systematically understand the adaptability of endosymbiont bacteria to host and special environment. Through the analysis of endosymbiont bacteria of Coleoptera insects in different saline-alkali areas in arid and semi-arid regions of Xinjiang, it was found that bacteria in different host samples were resistant to saline-alkali stress. These results suggest that bacteria and their hosts co-evolved in response to this climate. Therefore, this study is of great significance for understanding the endosymbiont bacteria of Coleoptera insects and obtaining extremophile resources (Saline-alkali-resistant chassis strains with modification potential for the production of bulk chemicals and highly robust industrial enzymes).

Rock types with similar lithological components and pore structures form the basic units of porous limestone reservoirs; this influences the reservoir evaluation efficiency and water injection development. As the main oil and gas pay zone in central Iraq, the Cretaceous Khasib Formation reservoirs are influenced by deposition, dissolution, and cementation. There is strong vertical heterogeneity in the most important zone of the Kh2 layer, with diverse rock types and complex pore structures. Based on core observation and casting thin-section identification, the Kh2 layer in the study area was divided into eight lithofacies types as argillaceous bioclastic wackestone, planktic foraminiferium wackestone, lamellar bioclastic wackestone, intraclastic–bioclastic packstone, patchy green algae packstone, green algae and pelletoid packstone, benthic foraminiferium–bioclastic packstone, and intraclastic grainstone. Along with the reservoir void space types of the lithofacies, capillary pressure curves are used to quantitatively analyze the throat and pore features of the different lithofacies. From the porosity–permeability cross-plot characteristics and distribution of pore types, 14 petrophysical facies are obtained. Finally, based on the differences between the lithofacies and petrophysical facies, the Kh2 member is divided into 13 rock types with different geological origins and petrophysical characteristics. Among these, the rock type RT1-8-14 has the best and rock type RT1-1-1 has the worst physical properties among the reservoir rock types. This study provides an optimization method for carbonate reservoir evaluation and is expected to be beneficial for efficient development of similar carbonate reservoirs.

Abstract Modulation of protein function through allosteric regulation is central in biology, but biomacromolecular systems involving multiple subunits and ligands may exhibit complex regulatory mechanisms at different levels, which remain poorly understood. Here, we discover an aldo-keto reductase termed AKRtyl and present its three-level regulatory mechanism. Specifically, by combining steady-state and transient kinetics, X-ray crystallography and molecular dynamics simulation, we demonstrate that AKRtyl exhibits a positive synergy mediated by an unusual Monod-Wyman-Changeux (MWC) paradigm of allosteric regulation at low concentrations of the cofactor NADPH, but an inhibitory effect at high concentrations is observed. While the substrate tylosin binds at a remote allosteric site with positive cooperativity. We further reveal that these regulatory mechanisms are conserved in AKR12D subfamily, and that substrate cooperativity is common in AKRs across three kingdoms of life. This work provides an intriguing example for understanding complex allosteric regulatory networks.

A dynamic plant architecture is the basis of plant adaptation to changing environments. Although many genes regulating leaf rolling have been identified, genes directly associated with water homeostasis are largely unknown. Here, we isolated a rice mutant, dynamic leaf rolling 1 (dlr1), characterized by ‘leaf unfolding in the morning-leaf rolling at noon-leaf unfolding in the evening’ during a sunny day. Water content was decreased in rolled leaves and water sprayed on leaves caused reopening, indicating that in vivo water deficiency induced the leaf rolling. Map-based cloning and expression tests demonstrated that an A1400G single base mutation in Oryza sativa Polygalacturonase 1 (OsPG1)/PHOTO-SENSITIVE LEAF ROLLING 1 (PSL1) was responsible for the dynamic leaf rolling phenotype in the dlr1 mutant. OsPG1 encodes a polygalacturonase, one of the main enzymes that degrade demethylesterified homogalacturonans in plant cell walls. OsPG1 was constitutively expressed in various tissues and was enriched in stomata. Mutants of the OsPG1 gene exhibited defects in stomatal closure and decreased stomatal density, leading to reduced transpiration and excessive water loss under specific conditions, but had normal root development. Further analysis revealed that mutation of OsPG1 led to reduced pectinase activity in the leaves and increased demethylesterified homogalacturonans in guard cells. Our findings reveal a mechanism by which OsPG1 modulates water homeostasis to control dynamic leaf rolling, providing insights for plants to adapt to environmental variation.

AbstractIn China, the concept of Museum Night Opening, which involves keeping museums open to the public beyond regular daytime hours, has gained popularity since its inception in 2019. However, its implementation has posed both social benefits and operational challenges. This study aims to develop management strategies for Museum Night Opening in China, using a regional perspective centered on Shanghai. A systematic review of Shanghai cases spanning from 2007 to August 2023 was conducted for the development status. A SWOT-TWOS analysis was further employed for the development environment and management strategies. The internal management strategies (WO & WT) emphasize aspects such as human resources, finance, and materials to ensure smooth night operations. Meanwhile, the external management strategies (SO & ST) focus on the audience orientation and crossover collaboration to enhance nighttime experiences. Through management strategy planning, Chinese museums can establish Museum Night Opening as a high-quality initiative in a sustainable manner.

Background Liquid biopsy, including the detection of circulating tumor cells (CTCs), has emerged as a promising tool for cancer diagnosis and monitoring. However, the prognostic value of CTCs in nasopharyngeal carcinoma (NPC) remains unclear due to the lack of phenotypic characterization. The expression of Excision Repair Cross-Complementation Group 1 (ERCC1) and CTCs epithelial-mesenchymal transition (EMT) have been associated with treatment efficacy. In this study, we aimed to evaluate the prognostic significance of ERCC1 expression on CTCs and their EMT subtypes before treatment in NPC. Methods We retrospectively analyzed 108 newly diagnosed locally advanced NPC patients who underwent CanPatrol™ CTC testing between November 2018 and November 2021. CTCs were counted and classified into epithelial, epithelial-mesenchymal hybrid, and mesenchymal subtypes. ERCC1 expression was divided into negative and positive groups. Clinical features and survival outcomes were analyzed. Results The positive rate of CTCs was 92.6% (100/108), with an ERCC1 positivity rate of 74% (74/100). Further analysis of the subtypes showed that positive ERCC1 on mesenchymal CTCs was associated with a later N stage ( P = .01). Positive ERCC1 expression was associated with poor overall survival (OS; P = .039) and disease-free survival (DFS; P = .035). Further analysis of subtypes showed that the positive ERCC1 on mesenchymal-type CTCs was associated with poor OS ( P = .012) and metastasis-free survival (MFS; P = .001). Conclusion Our findings suggest that ERCC1 expression on CTCs may serve as a new prognostic marker for NPC patients. Evaluating CTCs subtypes may become an auxiliary tool for personalized and precise treatment.

Abstract Background COVID‐19 has caused severe morbidity and mortality worldwide. After the end of the dynamic zero‐COVID policy in China in December, 2022, concerns regarding reinfection were raised while little was known due to the lack of surveillance data in this country. Aims This study reviews the probability, risk factors, and severity of severe acute respiratory syndrome coronavirus 2 Omicron variant reinfection, as well as the interval between infections, risk of onward transmission by reinfected cases, and the role of booster vaccination against reinfection. Sources References for this review were identified through searches of PubMed and Web of Science up to September 24, 2023. Results The rate of reinfection ranges from 3.1% to 13.0%. Factors associated with a higher risk of reinfection include being female, having comorbidities, and being unvaccinated. Reinfection with the BA.4 or BA.5 variant occurs approximately 180 days after the initial infection. Reinfections are less clinically severe than primary infections, and there is evidence of lower transmissibility. The debate surrounding the effectiveness and feasibility of booster vaccinations in preventing reinfection continues. Conclusions The reinfection rate during the Omicron epidemic is significantly higher than in previous epidemic periods. However, the symptoms and infectivity of reinfection were weaker than those of the prior infection. Medical staff and individuals at high risk of reinfection should be vigilant. The efficacy of booster vaccinations in reducing reinfection is currently under debate.

The effect of moisture on the fracture resistance of asphalt concrete is a significant concern in pavement engineering. To investigate the effect of the water vapor concentration on the fracture properties of asphalt concrete, this study first designed a humidity conditioning program at the relative humidity (RH) levels of 2%, 50%, 80%, and 100% for the three types of asphalt concrete mixtures (AC-13C, AC-20C, and AC-25C).The finite element model was developed to simulate the water vapor diffusion and determine the duration of the conditioning period. The semi-circular bending (SCB) test was then performed at varying temperatures of 5 °C, 15 °C, and 25 °C to evaluate the fracture energy and tensile strength of the humidity-conditioned specimens. The test results showed that the increasing temperature and the RH levels resulted in a lower peak load but greater displacement of the mixtures. Both the fracture energy and tensile strength tended to diminish with the rising temperature. It was also found that moisture had a significant effect on the tensile strength and fracture energy of asphalt concrete. Specifically, as the RH level increased from 2% to 100% (i.e., the water vapor concentration rose from 0.35 g/m3 to 17.27 g/m3), the tensile strength of the three types of mixtures was reduced by 34.84% on average, which revealed that the water vapor led to the loss of adhesion and cohesion within the mixture. The genetic expression programming (GEP) model was developed to quantify the effect of water vapor concentrations and temperature on the fracture indices.

In this study, the effect of chitosan-vanillin Schiff base emulsions (CSVAEs) on dough and bread characteristics was investigated. The results revealed that CSVAEs were embedded in the gluten and that the viscoelasticity and mechanical strength of the dough gradually increased with increasing CSVAEs concentration, α-helical and β-fold content, and elastic structure in the dough increased with the same patterns. The basic properties of bread were measured, and it was found that low concentrations of CSVAEs were effective in improving the quality of bread and slowing the staling rate. As the storage time increased, CSVAEs had less effect on the rate of moisture loss, hardness and springiness of the bread and more effect on the inhibition of the acidity of the bread. The addition of CSVAEs slowed the increase in bacteria and molds and extended the shelf life of the bread.

Fanconi anemia (FA)-mutated acute myeloid leukemia (AML) is a secondary AML with very poor prognosis and limited therapeutic options due to increased sensitivity to DNA-damaging agents. PD-1 immune checkpoint inhibitors upregulate T-cell killing of cancer cells and is a class of promising treatment for FA-AML. Here, we developed a novel FA-AML murine model that allows the study of human AML with a humanized immune system in order to investigate immunotherapeutic treatments in vivo. FA-AML1 cells and non-FA-mutated Kasumi-1 cells were injected into 8-10 week old NSG mice. Once leukemic engraftment was confirmed by HLA-DR expression in the peripheral blood, human peripheral blood mononuclear cells (hPBMCs) were injected into the mice. One week post-hPBMCs injection, Nivolumab (PD-1 inhibitor) or PBS vehicle control was administered to the mice bi-weekly. In our Nivolumab treated mice, FA-AML1, but not Kasumi-1-engrafted mice, had significantly prolonged overall survival. Both FA-AML1 and Kasumi-1 engrafted mice had decreased spleen weights. Higher leukemic infiltration into vital organs was observed in FA-AML1 engrafted mice compared to Kasumi-1 engrafted mice. In conclusion, our novel humanized murine model of FA-mutated AML is an attractive tool for supporting further studies and clinical trials using PD-1 inhibitors to treat FA-mutated AML.

Reservoir heterogeneity is one of the key factors affecting the exploration and development of oil and gas reservoirs. The Kh2 layer in the A field of Central Iraq is a major pay zone with strong longitudinal and lateral heterogeneity. The heterogeneity, controlled by geological factors, has not yet been confirmed, which seriously restricts the development of this pay zone. This study aims to establish a geological pattern for the reservoir heterogeneity of bioclastic limestone, providing a geological basis for heterogeneity evaluation. Based on the core observation, thin-section identification, and physical property analysis, the microfacies are classified, and the diagenetic sequences and the pore structure of the Kh2 layer are analyzed. Seven types of microfacies are developed in the Kh2 layer, namely, planktic foraminiferal wackestone (MFT1), lamellar bioclastic wackestone (MFT2), intraclastic–bioclastic packstone (MFT3), green algal packstone (MFT4), green alga–pelletoid packstone (MFT5), bioclastic–intraclastic packstone (MFT6), and intraclastic grainstone (MFT7). The heterogeneity of the different microfacies and heterogeneity within the same microfacies were evaluated using the variation coefficient of permeability tested from cores collected from wells and calculated by well-logging at different intervals. The highest heterogeneity was observed in the lamellar bioclastic wackestone (MFT2), with an average variation coefficient of 0.72. The lowest heterogeneity was observed in the green algal packstone (MFT4), with an average variation coefficient of 0.11. The vertical heterogeneity of the permeability is mainly controlled by sedimentation, while the lateral heterogeneity is mainly influenced by cementation, bioturbation, and the distribution of green algae. Finally, a micro-scale geological pattern for determining the reservoir heterogeneity of bioclastic limestone reservoirs is established. This study can guide the current injection development and remaining oil prediction in oilfields with similar backgrounds.

Tylosin is a 16-membered macrolide antibiotic widely used in veterinary medicine to control infections caused by Gram-positive pathogens and mycoplasmas. To improve the fermentation titer of tylosin in the hyperproducing Streptomyces xinghaiensis strain TL01, we sequenced its whole genome and identified the biosynthetic gene cluster therein. Overexpression of the tylosin efflux gene tlrC, the cluster-situated S-adenosyl methionine (SAM) synthetase gene metKcs, the SAM biosynthetic genes adoKcs-metFcs, or the pathway-specific activator gene tylR enhanced tylosin production by 18%, 12%, 11%, and 11% in the respective engineered strains TLPH08-2, TLPH09, TLPH10, and TLPH12. Co-overexpression of metKcs and adoKcs-metFcs as two transcripts increased tylosin production by 22% in the resultant strain TLPH11 compared to that in TL01. Furthermore, combinational overexpression of tlrC, metKcs, adoKcs-metFcs, and tylR as four transcripts increased tylosin production by 23% (10.93g/L) in the resultant strain TLPH17 compared to that in TL01. However, a negligible additive effect was displayed upon combinational overexpression in TLPH17 as suggested by the limited increment of fermentation titer compared to that in TLPH08-2. Transcription analyses indicated that the expression of tlrC and three SAM biosynthetic genes in TLPH17 was considerably lower than that of TLPH08-2 and TLPH11. Based on this observation, the five genes were rearranged into one or two operons to coordinate their overexpression, yielding two engineered strains TLPH23 and TLPH24, and leading to further enhancement of tylosin production over TLPH17. In particular, the production of TLPH23 reached 11.35 g/L. These findings indicated that the combinatorial strategy is a promising approach for enhancing tylosin production in high-yielding industrial strains.

Objective To explore the effectiveness of PDCA (Plan-Do-Check-Act Cycle Management) in clinical emergency blood management. Methods The data of emergency blood-using cases from January 2021 to June 2022 in each clinical department of our hospital were collected to observe the blood matching time, blood retrieving time, and emergency bloodusing rate. They were divided into PDCA experimental group (Experimental group, July to December 2021, n=287), pre-PDCA experimental group (Control group 1, January to June 2021, n=516) and post-PDCA experimental cessation group (Control group 2, January to June 2022, n=277). Subgroup analysis was performed according to different departments, which were Internal Medicine Department, Surgery Depatment, and ICU. The situation of non-emergency blood use occupying emergency lanes in the pre-implementation period was continuously improved using PDCA, and the differences in blood matching time, blood retrieving time, and emergency blood-using rate among the three groups were compared and analyzed by Kruskal-Wallis test and chi-square test. Results The blood matching time and blood retrieving time (M, min) in the experimental group, control group 1 and control group 2 were 19.00 vs 45.50 vs 23.00 and 22.00 vs 44.00 vs 25.00, respectively (P< 0.05), and were 19.00 vs 47.00 vs 24.00 and 23.00 vs 56.00 vs 30. 50 in Internal Medicine Department, 18.00 vs 57.50 vs 14.00 and 32.00 vs 41.00 vs 24.00 in Surgery Department, 20.00 vs 42.00 vs 23.00 and 16.50 vs 34.00 vs 12.50 in ICU (P

Abstract Background Streptomyces are well known for their potential to produce various pharmaceutically active compounds, the commercial development of which is often limited by the low productivity and purity of the desired compounds expressed by natural producers. Well-characterized promoters are crucial for driving the expression of target genes and improving the production of metabolites of interest. Results A strong constitutive promoter, stnYp, was identified in Streptomyces flocculus CGMCC4.1223 and was characterized by its effective activation of silent biosynthetic genes and high efficiency of heterologous gene expression. The promoter stnYp showed the highest activity in model strains of four Streptomyces species compared with the three frequently used constitutive promoters ermEp*, kasOp*, and SP44. The promoter stnYp could efficiently activate the indigoidine biosynthetic gene cluster in S. albus J1074, which is thought to be silent under routine laboratory conditions. Moreover, stnYp was found suitable for heterologous gene expression in different Streptomyces hosts. Compared with the promoters ermEp*, kasOp*, and SP44, stnYp conferred the highest production level of diverse metabolites in various heterologous hosts, including the agricultural-bactericide aureonuclemycin and the antitumor compound YM-216391, with an approximately 1.4 − 11.6-fold enhancement of the yields. Furthermore, the purity of tylosin A was greatly improved by overexpressing rate-limiting genes through stnYp in the industrial strain. Further, the yield of tylosin A was significantly elevated to 10.30 ± 0.12 g/L, approximately 1.7-fold higher than that of the original strain. Conclusions The promoter stnYp is a reliable, well-defined promoter with strong activity and broad suitability. The findings of this study can expand promoter diversity, facilitate genetic manipulation, and promote metabolic engineering in multiple Streptomyces species.

Fatigue cracking is one of the primary distresses of asphalt pavements, which significantly affects the asphalt pavement performance. The fatigue behavior of the asphalt mixture observed in the laboratory test can vary depending on the type of fatigue test and the dimension and shape of the test specimen. The variations can make it difficult to accurately evaluate the fatigue properties of the field asphalt concrete. Accordingly, this study proposed a reliable method to evaluate the fatigue behavior of the asphalt field cores based on discrete element modeling (DEM). The mesoscopic geometric model was built using discrete element software PFC (Particle Flow Code) and CT scan images of the asphalt field cores. The virtual fatigue test was simulated in accordance with the semi-circular bending (SCB) test. The mesoscopic parameters of the contacting model in the virtual test were determined through the uniaxial compression dynamic modulus test and SCB test. Based on the virtual SCB test, the displacement, contact forces, and crack growth were analyzed. The test results show that the fatigue life simulated in the virtual test was consistent with that of the SCB fatigue test. The fatigue cracks in the asphalt mixture were observed in three stages, i.e., crack initiation, crack propagation, and failure. It was found that the crack propagation stage consumes a significant portion of the fatigue life since the tensile contact forces mainly increase in this stage.

Abstract Background Carbamoyl phosphate synthetase I defect (CPS1D) is a rare disease with clinical case reports mainly in early neonates or adults, with few reports of first onset in late neonatal to childhood. We studied the clinical and genotypic characteristics of children with childhood onset CPS1D caused by two loci mutations (one of these is a rarely reported non-frame shift mutation) in the CPS1. Case presentation We present a rare case of adolescent-onset CPS1D that had been misdiagnosed due to atypical clinical features, and further investigations revealed severe hyperammonemia (287µmol/L; reference range 11.2 ~ 48.2umol/L). MRI of the brain showed diffuse white matter lesions. Blood genetic metabolic screening showed elevated blood alanine (757.06umol/L; reference range 148.8 ~ 739.74umol/L) and decreased blood citrulline (4.26umol/L; reference range 5.45 ~ 36.77umol/L). Urine metabolic screening showed normal whey acids and uracil. Whole-exome sequencing revealed compound heterozygous mutations in the CPS1, a missense mutation (c.1145 C > T) and an unreported de novo non-frame shift mutation (c.4080_c.4091delAGGCATCCTGAT), respectively, which provided a clinical diagnosis. Conclusion A comprehensive description of the clinical and genetic features of this patient, who has a rare age of onset and a relatively atypical clinical presentation, will facilitate the early diagnosis and management of this type of late onset CPS1D and reduce misdiagnosis, thus helping to reduce mortality and improve prognosis. It also provides a preliminary understanding of the relationship between genotype and phenotype, based on a summary of previous studies, which reminds us that it may help to explore the pathogenesis of the disease and contribute to genetic counselling and prenatal diagnosis.

Movement-specific vehicle classification and counting at traffic intersections is a crucial component of various traffic management activities. In this context, with recent advancements in computer-vision-based techniques, cameras have emerged as a reliable data source for extracting vehicular trajectories from traffic scenes. However, classifying these trajectories by movement type is quite challenging, as characteristics of motion trajectories obtained this way vary depending on camera calibrations. Although some existing methods have addressed such classification tasks with decent accuracies, the performance of these methods significantly relied on the manual specification of several regions of interest. In this study, we proposed an automated classification method for movement-specific classification (such as right-turn, left-turn and through movements) of vision-based vehicle trajectories. Our classification framework identifies different movement patterns observed in a traffic scene using an unsupervised hierarchical clustering technique. Thereafter, a similarity-based assignment strategy is adopted to assign incoming vehicle trajectories to identified movement groups. A new similarity measure was designed to overcome the inherent shortcomings of vision-based trajectories. Experimental results demonstrated the effectiveness of the proposed classification approach and its ability to adapt to different traffic scenarios without any manual intervention.

Abstract Background Fatty acids are involved in a wide range of immunological responses in humans. Supplementation of polyunsaturated fatty acids has been reported to help alleviate symptoms and airway inflammation in asthma patients, whereas the effects of fatty acids on the actual risk of asthma remain controversial. This study comprehensively investigated the causal effects of serum fatty acids on asthma risk using two-sample bidirectional Mendelian Randomization (MR) analysis. Methods Genetic variants strongly associated with 123 circulating fatty acid metabolites were extracted as instrumental variables, and a large GWAS data of asthma was used to test effects of the metabolites on this outcome. The inverse-variance weighted method was used for primary MR analysis. The weighted median, MR-Egger regression, MR-PRESSO, and leave-one-out analyses were utilized to evaluate heterogeneity and pleiotropy. Potential confounders were adjusted by performing multivariable MR analyses. Reverse MR analysis was also conducted to estimate the causal effect of asthma on candidate fatty acid metabolites. Further, we performed colocalization analysis to examine the pleiotropy of variants within the fatty acid desaturase 1 (FADS1) locus between the significant metabolite traits and the risk of asthma. Cis-eQTL-MR and colocalization analysis were also performed to determine the association between RNA expression of FADS1 and asthma. Results Genetically instrumented higher average number of methylene groups was causally associated with a lower risk of asthma in primary MR analysis, while inversely, the higher ratio of bis-allylic groups to double bonds and the higher ratio of bis-allylic groups to total fatty acids, were associated with higher probabilities of asthma. Consistent results were obtained in multivariable MR when adjusted for potential confounders. However, these effects were completely eliminated after SNPs correlated with the FADS1 gene were excluded. The reverse MR also found no causal association. The colocalization analysis suggested that the three candidate metabolite traits and asthma likely share causal variants within the FADS1 locus. In addition, the cis-eQTL-MR and colocalization analyses demonstrated a causal association and shared causal variants between FADS1 expression and asthma. Conclusions Our study supports a negative association between several PUFA traits and the risk of asthma. However, this association is largely attributed to the influence of FADS1 polymorphisms. The results of this MR study should be carefully interpreted given the pleiotropy of SNPs associated with FADS1.

Abstract Background Microglial polarization is one of the most promising therapeutic targets for multiple central nervous system (CNS) disorders, including ischemic stroke. However, detailed transcriptional alteration of microglia following cerebral ischemic stroke remains largely unclear. Methods Focal cerebral ischemia was induced by transient middle cerebral artery occlusion (tMCAO) for 60 min in mice. Single-cell RNA sequencing (scRNA-seq) was performed using ischemic brain tissues from tMCAO and sham mice 3 days after surgery. Ch25h −/− mice were used to investigate the role of specific microglia subcluster on post-stroke infarct volume and neuroinflammation. Results We identified a relatively homeostatic subcluster with enhanced antigen processing and three “ischemic stroke associated microglia” (ISAM): MKI67+, CH25H+ and OASL+ subclusters. We found the MKI67+ subcluster undergo proliferation and differentiation into CH25H+ and OASL+ subclusters. CH25H+ microglia was a critical subcluster of ISAM that exhibited increased phagocytosis and neuroprotective property after stroke. Ch25h −/− mice developed significantly increased infarct volume following ischemic stroke compared to Ch25h +/−. Meanwhile, the OASL+ subcluster accumulated in the ischemic brain and was associated with the evolving of neuroinflammation after stroke, which was further aggravated in the aged mice brain. Conclusions Our data reveal previously unrecognized roles of the newly defined CH25H+ and OASL+ microglia subclusters following ischemic stroke, with novel insights for precise microglia modulation towards stroke therapy.

Abstract Background To explore the gut microbiota characteristics in depressed patients with bipolar disorder (BD) as well as the connection between the gut microbiota and inflammatory markers. Methods Totally 72 depressed BD patients and 16 healthy controls (HCs) were enrolled in the study. Blood and feces samples were taken from each subject. With the help of 16S-ribosomal RNA gene sequencing, the characteristics of the gut microbiota in each participant were examined. Correlation analysis was then utilized to assess the relationship between the gut microbiota and clinical parameters. Results We found the taxonomic composition of the gut microbiota, but not its diversity, was significantly different in BD patients compared to HCs. We found the abundance of Bacilli, Lactobacillales and genus Veillonella were higher in BD patients than in HCs, while genus Dorea was more abundant in HCs. Additionally, correlation analysis showed that the bacterial genera’ abundance in BD patients was strongly correlated with the severity of depression and inflammatory markers. Conclusions According to these results, the gut microbiota characteristics were changed in depressed BD patients, which may have been associated with the severity of depression and the inflammatory pathways.

Full-film double-ridge furrow sowing technology (FDRFST) and nitrogen (N) management are crucial for sustainable agricultural development. To investigate the N fertilizer application scheme for spring maize with high yield, precipitation water productivity (PWP), and N use efficiency (NUE) under the FDRFST, a two-year field experiment was carried out in a rainfed area of Longzhong (LZ). Treatments included two types of N fertilization (common urea [U] and controlled release urea [CU]), three application rates (180, 225, and 270 kg hm−2), and the conditions of no N fertilizer application and no plastic film mulching. The results showed that the temperature-increase effect of PM on the soil between 2021 and 2022 was concentrated for 0–90 days, with average values of the 5 cm soil temperature increasing by 4.15 and 3.58 ºC, respectively. However, the N fertilizer application rate had negligible effects on soil temperature. Plastic film mulching (PM) required temperature-increase compensation, particularly during the sowing–emergence stage, with a 1.68 compensation coefficient. Based on the simulation results of the modified DNDC model, the recommended application rate of CU (180 kg hm−2) for spring maize in LZ increased the average yield, PWP, and NUE by 15.8%, 16.0%, and 36.4% from 1981 to 2020, respectively, compared to U treatments. Our results provide a theoretical basis for N management in spring maize production in LZ and offer critical insights for improving the DNDC model under PM conditions.

Environmental factors like temperature have a great impact on the predation potential of biological control agents. In the present study, the functional response of the predatory mite Neoseiulus californicus (Acari: Phytoseiidae) to the pest mite Tetranychus urticae (Acari: Tetranychidae) at moderate to high temperatures under laboratory conditions was determined. The study aimed to understand the prey-predator interaction under different temperatures and prey densities. Five constant temperatures (24 °C, 27 °C, 30 °C, 33 °C, and 36 °C), and thirteen prey densities (4, 5, 8, 10, 12, 15, 16, 20, 24, 25, 30, 32, and 40) of each stage (adult, nymph, larvae, and egg stage) were employed in the experiment. Observations were made 24 h after the start of each experiment. Results revealed that the predatory mites showed type II functional response to adult females of T. urticae, whereas type I to other stages (nymphs, larvae, and eggs) of T. urticae. The predation capability of adult predatory mites on T. urticae was significant at 24–36 °C. The instantaneous attack rate (a) of N. californicus increased and the handling time (Th) decreased with an increase in temperature. The maximum attack rate was recorded at 36 °C (1.28) for the egg stage. The longest handling time was (0.78) for the larval stage of T. urticae at 30 °C. Daily consumption increased with increasing prey density. Maximum daily consumption was observed at 33 °C (30.00) at the prey density of 40. Searching efficiency decreased with the increase in prey density but was found to increase with the rise in temperature. N. californicus was found to be voracious on the larval and egg stages. Conclusively, the incorporation of N. californicus at earlier stages (larvae and eggs) of T. urticae would be beneficial under warm conditions because managing a pest at its initial stage will save the crop from major losses. The results presented in this study at various temperatures will be helpful in different areas with different temperature extremes. The results of the functional response can also be applied to mass rearing, quality testing, and integrated pest management programmes.

Background Bactrocera minax (Enderlein, 1920) (Diptera: Tephritidae) is a destructive citrus pest. It is mainly distributed throughout Shaanxi, Sichuan, Chongqing, Guizhou, Yunnan, Hubei, Hunan, and Guangxi in China and is considered to be a second-class pest that is prohibited from entering that country. Climate change, new farming techniques, and increased international trade has caused the habitable area of this pest to gradually expand. Understanding the suitable habitats of B. minax under future climate scenarios may be crucial to reveal the expansion pattern of the insect and develop corresponding prevention strategies in China. Methods Using on the current 199 distribution points and 11 environmental variables for B. minax, we chose the optimal MaxEnt model to screen the dominant factors that affect the distribution of B. minax and to predict the potential future distribution of B. minax in China under two shared socio-economic pathways (SSP1-2.6, SSP5-8.5). Results The current habitat of B. minax is located at 24.1–34.6°N and 101.1–122.9°E, which encompasses the provinces of Guizhou, Sichuan, Hubei, Hunan, Chongqing, and Yunnan (21.64 × 104 km2). Under future climate scenarios, the potential suitable habitat for B. minax may expand significantly toward the lower-middle reaches of the Yangtze River. The land coverage of highly suitable habitats may increase from 21.64 × 104 km2 to 26.35 × 104 × 104 km2 (2050s, SSP5-8.5) ~ 33.51 × 104 km2 (2090s, SSP5-8.5). This expansion area accounts for 29% (2050s, SSP1-2.6) to 34.83% (2090s, SSP1-2.6) of the current habitat. The center of the suitable habitat was predicted to expand towards the northeast, and the scenario with a stronger radiative force corresponded to a more marked movement of the center toward higher latitudes. A jackknife test showed that the dominant variables affecting the distribution of B. minax were the mean temperature of the driest quarter (bio9), the annual precipitation (bio12), the mean diurnal range (bio2), the temperature annual range (bio7), and the altitude (alt). Discussion Currently, it is possible for B. minax to expand its damaging presence. Regions with appropriate climate conditions and distribution of host plants may become potential habitats for the insects, and local authorities should strengthen their detection and prevention strategies. Climate changes in the future may promote the survival and expansion of B. minax species in China, which is represented by the significant increase of suitable habitats toward regions of high altitudes and latitudes across all directions but with some shrinkage in the east and west sides.

This paper aims to study the impact of human resource heterogeneity on firms’ cash-holding policies. The authors construct a proxy for human resource heterogeneity using the dissimilarity in employees’ skill structure between the firm and its peers in the same industry. The authors report evidence that firms with heterogeneous human resources hold more cash than other firms. This effect is more pronounced in labor-intensive firms and firms more susceptible to hold-up by employees, i.e. firms located in regions with more labor disputes and firms surrounded by more external employment opportunities. In addition, the authors demonstrate that high cash holdings triggered by human resource heterogeneity reduce the scale and efficiency of firms’ capital investment. This study highlights the role of human resource heterogeneity in determining firms’ cash policies. This paper adds to the understanding of labor adjustment costs within the firm and provides insights into firms’ cash-holding decisions.

Natural antimicrobial metabolites produced by soil microorganisms can be used as green pesticides. Here, the authors isolated a Pseudomonas mosselii strain 923 from rice rhizosphere soils and identify the compound pyrazolotriazine pseudoiodinine inhibits the growth of plant bacterial and fungal pathogens.

Chaotic systems are widely used in various aspects such as information security, signal processing, and synchronous control. The structural complexity and the chaotic behavior of chaotic systems are two significant factors affecting their practical applications. In this paper, we propose a universal two-dimensional (2D) absolute-cosine chaotic model (ACCM). The 2D-ACCM is composed of a nonlinear bounded cosine function and an absolute value function. It can construct new chaotic maps with simple structures and complex chaotic behaviors on the basis of existing chaotic systems. To verify the effectiveness of the proposed system, we first choose two existing one-dimensional (1D) chaotic maps and one existing 2D chaotic map as the seed maps of the 2D-ACCM to generate two new maps, respectively. The results of chaotic behavior analysis show that these two new maps have more complex chaotic behavior and wider chaotic ranges than seed maps and some advanced chaotic maps. Then a hardware experiment platform based on a field-programmable gate array (FPGA) is used for the hardware implementation of the new maps. Finally, a simple chaos-based pseudo-random number generator (PRNG) is introduced to show the practical application. The experimental results show that the new maps can be easily implemented on the FPGA and the chaos-PRNGs can generate pseudo-random numbers with excellent randomness.

Abstract Background Although child maltreatment (CM) experiences are recognized risk factors for nonsuicidal self-injury (NSSI), the mechanisms underlying this relationship remain unclear. The purpose of this study was to examine whether difficulty in emotion regulation (DER) and depressive symptoms mediate the relationship between child maltreatment experiences and NSSI severity, adjusting for demographic variables. Methods The participants were 224 adolescent inpatients recruited from a hospital in China (mean age 15.30 years, SD = 1.83; 78.6% females). Study measures included the Clinician-Rated Severity of Nonsuicidal Self-Injury (CRSNSSI), Childhood Trauma Questionnaire (CTQ-SF), Difficulties in Emotion Regulation Scale (DERS), and Patient Health Questionnaire-9 (PHQ-9). The hypothesized chain mediation model was tested using the structural equation model. Results A total of 146 (65.18%) adolescents reported engaging in NSSI during the past 12 months, and 103 (45.98%) participants met the DSM-5 diagnostic criteria for NSSI. Emotional neglect (48.1%) and emotional abuse (46.1%) had the highest prevalence, followed by physical neglect (43.1%) and physical abuse (24.1%), whereas sexual abuse (12.5%) was the least prevalent form of CM. Separately, both DER and depressive symptoms significantly mediated the association between CM and NSSI, with DER being the strongest mediator, with an indirect effect of 49.40% (p = 0.014). At the same time, we also proved a potential chain-mediated pathway of DER and depression in the relationship between CM and NSSI. Conclusion Child maltreatment seems to play a role in the aetiology of NSSI. DER and depressive symptoms both have a mediating role in the relationship between CM and NSSI. Importantly, DER seems to be a mediator with a stronger indirect effect compared to depressive symptoms.

Abstract Objective The efficacy and safety of epinephrine in patients with out-of-hospital cardiac arrest (OHCA) remains controversial. The meta-analysis was used to comprehensively appraise the influence of epinephrine in OHCA patients. Methods We searched all randomized controlled and cohort studies published by PubMed, EMBASE, and Cochrane Library from the inception to August 2022 on the prognostic impact of epinephrine on patients with OHCA. Survival to discharge was the primary outcome, while the return of spontaneous circulation (ROSC) and favorable neurological outcome were secondary outcomes. Results The meta-analysis included 18 studies involving 863,952 patients. OHCA patients with adrenaline had an observably improved chance of ROSC (RR 2.81; 95% CI 2.21–3.57; P = 0.001) in randomized controlled studies, but the difference in survival to discharge (RR 1.27; 95% CI 0.58–2.78; P = 0.55) and favorable neurological outcomes (RR 1.21; 95% CI 0.90–1.62; P = 0.21) between the two groups was not statistically significant. In cohort studies, the rate of ROSC (RR 1.62; 95% CI 1.14–2.30; P = 0.007) increased significantly with the adrenaline group, while survival to discharge (RR 0.73; 95% CI 0.55–0.98; P = 0.03) and favorable cerebral function (RR 0.42; 95% CI 0.30–0.58; P = 0.001) were lower than the non-adrenaline group. Conclusion We found that both the randomized controlled trials (RCTs) and cohort studies showed that adrenaline increased ROSC in OHCA patients. However, they were unable to agree on a long-term prognosis. The cohort studies showed that adrenaline had an adverse effect on the long-term prognosis of OHCA patients (discharge survival rate and good neurological prognosis), but adrenaline had no adverse effect in the RCTs. In addition to the differences in research methods, there are also some potential confounding factors in the included studies. Therefore, more high-quality studies are needed to fully confirm the effect of adrenaline on the long-term results of OHCA.

The fouling of separation membranes has consistently been a primary factor contributing to the decline in membrane performance. Enhancing the surface hydrophilicity of the membrane proves to be an effective strategy in mitigating membrane fouling in water treatment processes. Zwitterionic polymers (containing an equimolar number of homogeneously distributed anionic and cationic groups on the polymer chains) have been used extensively as one of the best antifouling materials for surface modification. The conventional application of zwitterionic compounds as surface modifiers is intricate and inefficient, adding complexity and length to the membrane preparation process, particularly on an industrial scale. To overcome these limitations, zwitterionic polymer, directly used as a main material, is an effective method. In this work, a novel zwitterionic polymer (TB)—zwitterionic Tröger’s base (ZTB)—was synthesized by quaternizing Tröger’s base (TB) with 1,3-propane sultone. The obtained ZTB is blended with TB to fabricate microfiltration (MF) membranes via the vapor-induced phase separation (VIPS) process, offering a strategic solution for separating emulsified oily wastewater. Atomic force microscopy (AFM), scanning electron microscopy (SEM), water contact angle, and zeta potential measurements were employed to characterize the surface of ZTB/TB blended membranes, assessing surface morphology, charge, and hydrophilic/hydrophobic properties. The impact of varying ZTB levels on membrane surface morphology, hydrophilicity, water flux, and rejection were investigated. The results showed that an increase in ZTB content improved hydrophilicity and surface roughness, consequently enhancing water permeability. Due to the attraction of water vapor, the enrichment of zwitterionic segments was enriched, and a stable hydration layer was formed on the membrane surface. The hydration layer formed by zwitterions endowed the membrane with good antifouling properties. The proposed mechanism elucidates the membrane’s proficiency in demulsification and the reduction in irreversible fouling through the synergistic regulation of surface charge and hydrophilicity, facilitated by electrostatic repulsion and the formation of a hydration layer. The ZTB/TB blended membranes demonstrated superior efficiency in oil–water separation, achieving a maximum flux of 1897.63 LMH bar−1 and an oil rejection rate as high as 99% in the oil–water emulsion separation process. This study reveals the migration behavior of the zwitterionic polymer in the membrane during the VIPS process. It enhances our comprehension of the antifouling mechanism of zwitterionic membranes and provides guidance for designing novel materials for antifouling membranes.

Background and aims: Certain chromosomal structural variations (SVs) in biological parents can lead to recurrent spontaneous abortions (RSAs). Unequal crossing over during meiosis can result in the unbalanced rearrangement of gamete chromosomes such as duplication or deletion. Unfortunately, routine techniques such as karyotyping, fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA), and copy number variation sequencing (CNV-seq) cannot detect all types of SVs. In this study, we show that optical genome mapping (OGM) quickly and accurately detects SVs for RSA patients with a high resolution and provides more information about the breakpoint regions at gene level.Methods: Seven couples who had suffered RSA with unbalanced chromosomal rearrangements of aborted embryos were recruited, and ultra-high molecular weight (UHMW) DNA was isolated from their peripheral blood. The consensus genome map was created by de novo assembly on the Bionano Solve data analysis software. SVs and breakpoints were identified via alignments of the reference genome GRCh38/hg38. The exact breakpoint sequences were verified using either Oxford Nanopore sequencing or Sanger sequencing.Results: Various SVs in the recruited couples were successfully detected by OGM. Also, additional complex chromosomal rearrangement (CCRs) and four cryptic balanced reciprocal translocations (BRTs) were revealed, further refining the underlying genetic causes of RSA. Two of the disrupted genes identified in this study, FOXK2 [46,XY,t(7; 17)(q31.3; q25)] and PLXDC2 [46,XX,t(10; 16)(p12.31; q23.1)], had been previously shown to be associated with male fertility and embryo transit.Conclusion: OGM accurately detects chromosomal SVs, especially cryptic BRTs and CCRs. It is a useful complement to routine human genetic diagnostics, such as karyotyping, and detects cryptic BRTs and CCRs more accurately than routine genetic diagnostics.

Dietary fibers (DFs) and their metabolites attract significant attention in research on health and disease, attributing to their effects on regulating metabolism, proliferation, inflammation, and immunity. When fermented by gut microbiota, DFs mainly produce short-chain fatty acids (SCFAs), such as acetic acid, propionic acid, and butyric acid. As the essential nutrients for intestinal epithelial cells, SCFAs maintain intestinal homeostasis and play essential roles in a wide range of biological functions. SCFAs have been found to inhibit histone deacetylase, activate G protein-coupled receptors, and modulate the immune response, which impacts cancer and anti-cancer treatment. Notably, while extensive studies have illuminated the roles of SCFAs in colorectal cancer development, progression, and treatment outcomes, limited evidence is available for other types of cancers. This restricts our understanding of the complex mechanisms and clinical applications of SCFAs in tumors outside the intestinal tract. In this study, we provide a comprehensive summary of the latest evidence on the roles and mechanisms of SCFAs, with a focus on butyric acid and propionic acid, derived from microbial fermentation of DFs in cancer. Additionally, we recapitulate the clinical applications of SCFAs in cancer treatments and offer our perspectives on the challenges, limitations, and prospects of utilizing SCFAs in cancer research and therapy.

Commercial koji has been increasingly used in Chinese Baijiu brewing; however, there are only few studies comparing different koji and their relationship with key components of Chinese Baijiu such as ethyl acetate, ethyl lactate, and higher alcohols. Here, we studied six commercially available koji and showed that the microbial communities in the individual koji varied in composition, with Rhizopus, Aspergillus, and Bacillus primarily associated with starch hydrolysis and Saccharomyces mainly associated with alcohol production. In the brewing processes using the six koji, Saccharomyces was undoubtedly the most abundant fungus and Weissella, Bacillus, and Acinetobacter were the predominant bacterial groups. The levels of ethyl acetate, ethyl lactate, and higher alcohols in all brewing processes using the koji exhibited rapid increase in the early stages of fermentation, which stabilized in the later stages, followed by substantial increase after distillation. The results of metagenomic and redundancy analyses of samples taken during the brewing processes indicated that Saccharomyces from the koji was closely related to the production of ethyl acetate, ethyl lactate, and higher alcohols. This study provides a basis for the quality improvement and application of commercial koji.

In order to study the changes of storage quality of red Amygdalus persica treated with melatonin and eugenol, the red Amygdalus persica was used as the experimental material in this experiment. Different treatments (0.5 mmol/L melatonin treatment; 50 µL/L eugenol treatment; 0.5 mmol/L melatonin+50 µL/L eugenol treatment) were used to soak the red Amygdalus persica for 5 min. After treatment, it was naturally dried and stored at a temperature of (0.5±0.5) ℃ to study the quality changes of red Amygdalus persica during storage. The results showed that: Melatonin combined with eugenol treatment could effectively reduce fruit decay rate and respiratory intensity, and delay the decline of firmness, soluble solid content, titratable acid content and total phenol content, effectively maintained SOD activity, APX and PPO activity. At 60 days of storage, the fruit decay rate of melatonin combined with eugenol group was only 14.65%, while that of CK group, melatonin group and eugenol group were 36.72%, 25.63% and 22.49% respectively. In conclusion, melatonin combined with eugenol treatment could delay fruit softening, inhibit the decline of fruit quality and significantly prolong the storage period of fruits.

In the experiment, used Xinjiang Tianshan Special Flour and related additives as raw materials with shear force (ductility, hardness, chewability) and cooking characteristics (water absorption index, cooking loss rate), starch gelatinization degree and sensory evaluation as evaluation indices. The effects on microwave firepower, steam microwave curing time and steam quantity on dough slice quality, on the basis, the steam microwave curing process was optimized by combining response surface and principal component analysis. The results show that: Under the conditions of 60% microwave power, 3 min steam microwave curing time and 12 L steam quantity, ductility was 98.155 g·s, hardness was 2204.46 g, chewability was 5200.52 g·s, water absorption index was 142.516%, cooking loss rate was 2.79%, sensory score was 91.8 and standardized score was 0.946, which were basically consistent with the predicted value. Through the experiment, steam microwave curing process was optimized by response surface analysis (RSM) and principal component analysis (PCA), which had guiding significance for practical production.

Klinefelter syndrome (KS) is a leading contributor to male infertility and is characterised by complex and diverse clinical features; however, genetic changes in the KS transcriptome remain largely unknown. We therefore used transcriptomic and single‐cell RNA sequencing (scRNA‐seq) datasets from KS versus normal populations through the Gene Expression Omnibus (GEO) database to identify gene biomarkers associated with the occurrence of KS. We identified a total of 700 differentially expressed genes (DEGs) and completed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), enrichment pathway analysis and protein‐protein interaction (PPI) network analysis. A total of four unreported KS‐related hub genes (KIF2C, MRPS2, RPS15 and TSFM) were identified. Validation of the single‐cell sequencing dataset showed that only KIF2C and RPS15 were expressed in spermatocytes and that they were differentially expressed in sperm cells. Further construction of the developmental trajectories of these two genes in sperm cells showed that the KIF2C gene showed an upward trend throughout the differentiation and development of sperm cells. In conclusion, we report here that KIF2C may be closely related to the differentiation and development of sperm cells in KS patients, which is important for revealing the molecular mechanism of KS and conducting further studies.

‘Protein arginine methyltransferase 5 (PRMT5) is known to regulate the expression of genes involved in metastasis. Here, the authors show that PRMT5 methylates Akt and methylation is required for phosphorylation and activation of Akt; ultimately leading to the increase in expression of pro-metastatic transcription factors.

Epstein-Barr virus (human herpesvirus 4, EBV) is a linear double-stranded DNA virus that infects over 90% of the population worldwide. However, our understanding of EBV’s contribution to tumorigenesis of EBV-associated GC (EBVaGC) remains incomplete. Recent advancements in EBVaGC research have highlighted that EBV-encoded microRNAs (miRNAs) play prominent roles in critical cellular processes such as migration, cell cycle, apoptosis, cell proliferation, immune response, and autophagy. Notably, the largest group of EBV-encoded miRNAs, known as BamHI-A rightward transcripts (BARTs), exhibit bidirectional effects in EBVaGC. For instance, they present both anti-apoptotic and pro-apoptotic functions and enhance chemosensitivity while also conferring resistance to 5-fluorouracil. Despite these findings, the comprehensive mechanisms through which miRNAs contribute to EBVaGC are yet to be fully elucidated. In this work, we summarize the current evidence of the roles of miRNA in EBVaGC, particularly with the application of multi-omic techniques. Additionally, we discuss the application of miRNA in EBVaGC in retrospective analyses and provide novel perspectives on the use of miRNA in EBVaGC in translational medicine.

Substantial improvement in prognosis among metastatic renal cell carcinoma (mRCC) patients has been achieved, owing to the rapid development and utilization of immunotherapy. In particular, immune checkpoint inhibitors (ICIs) have been considered the backbone of systemic therapy for patients with mRCC alongside multi-targeted tyrosine kinase inhibitors (TKIs) in the latest clinical practice guidelines. However, controversies and challenges in optimal individualized treatment regarding immunotherapy remains still About 2/3 of the patients presented non-response or acquired resistance to ICIs. Besides, immune-related toxicities, namely immune-related adverse events, are still elusive and life-threatening. Thus, reliable biomarkers to predict immunotherapeutic outcomes for mRCC patients are needed urgently. Tumor microenvironment (TME), consisting of immune cells, vasculature, signaling molecules, and extracellular matrix and regulates tumor immune surveillance and immunological evasion through complex interplay, plays a critical role in tumor immune escape and consequently manipulates the efficacy of immunotherapy. Various studied have identified the different TME components are significantly associated with the outcome of mRCC patients receiving immunotherapy, making them potential valuable biomarkers in therapeutic guidance. The present review aims to summarize the latest evidence on the associations between the components of TME including immune cells, cytokines and extracellular matrix, and the therapeutic responses among mRCC patients with ICI-based treatment. We further discuss the feasibility and limitation of these components as biomarkers.

Inflammasome activation is an essential innate immune defense mechanism against Salmonella infections. Salmonella has developed multiple strategies to avoid or delay inflammasome activation, which may be required for long-term bacterial persistence. However, the mechanisms by which Salmonella evades host immune defenses are still not well understood. In this study, Salmonella Enteritidis (SE) random insertion transposon library was screened to identify the key factors that affect the inflammasome activation. The type I secretion system (T1SS) protein SiiD was demonstrated to repress the NLRP3 inflammasome activation during SE infection and was the first to reveal the antagonistic role of T1SS in the inflammasome pathway. SiiD was translocated into host cells and localized in the membrane fraction in a T1SS-dependent and partially T3SS-1-dependent way during SE infection. Subsequently, SiiD was demonstrated to significantly suppress the generation of mitochondrial reactive oxygen species (mtROS), thus repressing ASC oligomerization to form pyroptosomes, and impairing the NLRP3 dependent Caspase-1 activation and IL-1β secretion. Importantly, SiiD-deficient SE induced stronger gut inflammation in mice and displayed NLRP3-dependent attenuation of the virulence. SiiD-mediated inhibition of NLRP3 inflammasome activation significantly contributed to SE colonization in the infected mice. This study links bacterial T1SS regulation of mtROS-ASC signaling to NLRP3 inflammasome activation and reveals the essential role of T1SS in evading host immune responses.

Bacterial infection is a major challenge that could threaten the patient’s life in repairing bone defects with implant materials. Developing functional scaffolds with an intelligent antibacterial function that can be used for bone repair is very important. We constructed a drug delivery (HA@TA-CS/SA) scaffold with curcumin-loaded dendritic mesoporous organic silica nanoparticles (DMON@Cur) via 3D printing for antibacterial bone repair. Inspired by the adhesion mechanism of mussels, the HA@TA-CS/SA scaffold of hydroxyapatite (HA) and chitosan (CS) is bridged by tannic acid (TA), which in turn binds sodium alginate (SA) using electrostatic interactions. The results showed that the HA@TA-CS/SA composite scaffold had better mechanical properties compared with recent literature data, reaching 68.09 MPa. It displayed excellent degradation and mineralization capabilities with strong biocompatibility in vitro. Furthermore, the antibacterial test results indicated that the curcumin-loaded scaffold inhibited S.aureus and E.coli with 99.99% and 96.56% effectiveness, respectively. These findings show that 3D printed curcumin-loaded HA@TA-CS/SA scaffold has considerable promise for bone tissue engineering.

Enterobactin is an archetypical catecholate siderophore that plays a key role in the acquisition of ferric iron by microorganisms. Catechol moieties have been shown to be promising siderophore cores. Variants of the conserved 2,3-dihydroxybenzoate (DHB) moiety with structural modifications expand the bioactivity. Streptomyces are characterized by metabolites with diverse structures. The genomic sequence of Streptomyces varsoviensis indicated that it possessed a biosynthetic gene cluster for DHB containing siderophores and metabolic profiling revealed metabolites correlated with catechol-type natural products. Here, we report the discovery of a series of catecholate siderophores produced by S. varsoviensis and a scale-up fermentation was performed to purify these compounds for structural elucidation. A biosynthetic route for the catecholate siderophores is also proposed. These new structural features enrich the structural diversity of the enterobactin family compounds. One of the new linear enterobactin congeners shows moderate activity against a food-borne pathogen Listeria monocytogenes. This work demonstrated that changing culture conditions is still a promising approach to explore unexplored chemical diversity. The availability of the biosynthetic machinery will enrich the genetic toolbox of catechol siderophores and facilitate such engineering efforts.

In this study, the cobalt-chromium-molybdenum (CoCrMo) alloys containing varying Cu contents (CCM-xCu, x = 0, 2, 3, 4 wt%) were fabricated via the selected laser melting (SLM) method. The influences of Cu content on tribological performance and corrosion resistance were investigated. The 2 and 3 wt% Cu contributed to inhibiting the generation of the HCP phase, whereas the inhibitory effect was quite limited at 4 wt% Cu. Notably, 4 wt% Cu led to the formation of Cr-enrich precipitates in the matrix, which was partially coherent with the Cu nanoparticle. The corrosion resistance of the CCM alloy was enhanced as the 2 and 3 wt% Cu added into the CCM alloy, contrarily, which deteriorated when Cu content reached 4 wt%. For the CCM-2Cu and CCM-3Cu, Cr-precipitates played a major role in enhancing the wear resistance, while the Cu lubrication effect working in coordination with Cr-precipitates determined that for the CCM-4Cu. This study was expected to achieve better tribology and corrosion properties of SLM-produced CCM alloys by tailoring microstructure through the Cu element.

The dough slice was cooked by steam microwave, the influences of microwave drying (MD), hot air drying (HD), microwave-hot air combined drying (MD-HAD), microwave-vacuum combined drying (MVD) and vacuum-freeze combined drying (VD-FD) on the drying characteristics, shear force, boiling characteristics, microstructure and organoleptic evaluation of the dough slice were researched. The results indicated that the water loss rate of the dough slice was MVD>MD>MD-HAD>HD, and the drying of the dough slice of MVD was completed in only 30 min under the conditions of minimum power, maximum load and vacuum degree. According to the shear force and boiling characteristics, MD was a better drying method, and the rehydration time was only 359.667 s. According to the microstructure, the quality of the dough slice was as following: VD-FD>MD>MVD>HD>MD-HAD. The cross section of MD dough slice had more and larger voids, which was favorable for shortening the rehydration time. The cross section of VD-FD dough slice had less voids, the size was uniform, and the distribution was uniform. According to the comprehensive sensory evaluation, the palatability, toughness, viscosity and comprehensive sensory score of MD dough slice are relatively high, indicating its good quality.