Search

Abstract Background RNA sequencing (RNA-seq) is widely used for gene expression profiling and quantification. Quantitative RNA sequencing usually requires cell counting and spike-in, which is not always applicable to many samples. Here, we present a novel quantitative RNA sequencing method independent of spike-ins or cell counting, named siqRNA-seq, which can be used to quantitatively profile gene expression by utilizing gDNA as an internal control. Single-stranded library preparation used in siqRNA-seq profiles gDNA and cDNA with equal efficiency. Results To quantify mRNA expression levels, siqRNA-seq constructs libraries for total nucleic acid to establish a model for expression quantification. Compared to Relative Quantification RNA-seq, siqRNA-seq is technically reliable and reproducible for expression profiling but also can sequence reads from gDNA which can be used as an internal reference for accurate expression quantification. Applying siqRNA-seq to investigate the effects of actinomycin D on gene expression in HEK293T cells, we show the advantages of siqRNA-seq in accurately identifying differentially expressed genes between samples with distinct global mRNA levels. Furthermore, we analyzed factors influencing the downward trend of gene expression regulated by ActD using siqRNA-seq and found that mRNA with m6A modification exhibited a faster decay rate compared to mRNA without m6A modification. Additionally, applying this technique to the quantitative analysis of seven tumor cell lines revealed a high degree of diversity in total mRNA expression among tumor cell lines. Conclusions Collectively, siqRNA-seq is a spike-in independent quantitative RNA sequencing method, which creatively uses gDNA as an internal reference to absolutely quantify gene expression. We consider that siqRNA-seq provides a convenient and versatile method to quantitatively profile the mRNA landscape in various samples.

Abstract Pityriasis rubra pilaris (PRP) is an inflammatory papulosquamous dermatosis, characterized by hyperkeratotic follicular papules and erythematous desquamative plaques. The precise pathogenic mechanism underlying PRP remains incompletely understood. Herein, we conduct a case-control study involving a cohort of 102 patients with sporadic PRP and 800 healthy controls of Han Chinese population and identify significant associations (P = 1.73 × 10−6) between PRP and heterozygous mutations in the Keratin 32 gene (KRT32). KRT32 is found to be predominantly localized in basal keratinocytes and exhibits an inhibitory effect on skin inflammation by antagonizing the NF-κB pathway. Mechanistically, KRT32 binds to NEMO, promoting excessive K48-linked polyubiquitination and NEMO degradation, which hinders IKK complex formation. Conversely, loss-of-function mutations in KRT32 among PRP patients result in NF-κB hyperactivation. Importantly, Krt32 knockout mice exhibit a PRP-like dermatitis phenotype, suggesting compromised anti-inflammatory function of keratinocytes in response to external pro-inflammatory stimuli. This study proposes a role for KRT32 in regulating inflammatory immune responses, with damaging variants in KRT32 being an important driver in PRP development. These findings offer insights into the regulation of skin immune homeostasis by keratin and open up the possibility of using KRT32 as a therapeutic target for PRP.

Abstract Bullous pemphigoid (BP) is a type 2 inflammation- and immunity-driven skin disease, yet a comprehensive understanding of the immune landscape, particularly immune-stromal crosstalk in BP, remains elusive. Herein, using single-cell RNA sequencing (scRNA-seq) and in vitro functional analyzes, we pinpoint Th2 cells, dendritic cells (DCs), and fibroblasts as crucial cell populations. The IL13-IL13RA1 ligand–receptor pair is identified as the most significant mediator of immune-stromal crosstalk in BP. Notably, fibroblasts and DCs expressing IL13RA1 respond to IL13-secreting Th2 cells, thereby amplifying Th2 cell-mediated cascade responses, which occurs through the specific upregulation of PLA2G2A in fibroblasts and CCL17 in myeloid cells, creating a positive feedback loop integral to immune-stromal crosstalk. Furthermore, PLA2G2A and CCL17 contribute to an increased titer of pathogenic anti-BP180-NC16A autoantibodies in BP patients. Our work provides a comprehensive insight into BP pathogenesis and shows a mechanism governing immune-stromal interactions, providing potential avenues for future therapeutic research.

Abstract Although Prussian blue nanozymes (PBNZ) are widely applied in various fields, their catalytic mechanisms remain elusive. Here, we investigate the long-term catalytic performance of PBNZ as peroxidase (POD) and catalase (CAT) mimetics to elucidate their lifespan and underlying mechanisms. Unlike our previously reported Fe3O4 nanozymes, which exhibit depletable POD-like activity, the POD and CAT-like activities of PBNZ not only persist but slightly enhance over prolonged catalysis. We demonstrate that the irreversible oxidation of PBNZ significantly promotes catalysis, leading to self-increasing catalytic activities. The catalytic process of the pre-oxidized PBNZ can be initiated through either the conduction band pathway or the valence band pathway. In summary, we reveal that PBNZ follows a dual-path electron transfer mechanism during the POD and CAT-like catalysis, offering the advantage of a long service life.

Abstract Background Tuberculosis (TB) remains a global public health event of great concern, however epidemic data on TB covering entire areas during the special period of the COVID-19 epidemic have rarely been reported. We compared the dissemination and multidrug-resistance patterns of Mycobacterium tuberculosis complex (MTBC) in the main urban area of Luoyang City, China (including six municipal jurisdictions) and nine county and township areas under its jurisdiction, aimed to establish the epidemiology of TB in this region and to provide reference for precision anti-TB in places with similar settings. Methods From 2020 to 2022, sputum samples were collected from 18,504 patients with confirmed, suspected and unexcluded TB in 10 designated TB medical institutions. Insertion sequence 6110 was amplified by PCR (rpoB gene detection if necessary) to confirm the presence of MTBC. PCR-positive specimens were analyzed by multicolor melting curve analysis to detect multidrug resistance. Results Among the 18,504 specimens, 2675 (14.5%) were MTBC positive. The positive rate was higher in the main urban area than in the county and township areas (29.8% vs. 10.9%, p 60 years were the largest group infected with MTBC in the main urban area, compared with individuals aged

Acute myeloid leukemia (AML), as the most common malignancy of the hematopoietic system, poses challenges in treatment efficacy, relapse, and drug resistance. In this study, we have utilized 151 RNA sequencing datasets, 194 DNA methylation datasets, and 200 somatic mutation datasets from the AML cohort in the TCGA database to develop a multi-omics stratification model. This model enables comparison of prognosis, clinical features, gene mutations, immune microenvironment and drug sensitivity across subgroups. External validation datasets have been sourced from the GEO database, which includes 562 mRNA datasets and 136 miRNA datasets from 984 adult AML patients. Through multi-omics-based stratification model, we classified 126 AML patients into 4 clusters (CS). CS4 had the best prognosis, with the youngest age, highest M3 subtype proportion, fewest copy number alterations, and common mutations in WT1, FLT3, and KIT genes. It showed sensitivity to HDAC inhibitors and BCL-2 inhibitors. Both the M3 subtype and CS4 were identified as independent protective factors for survival. Conversely, CS3 had the worst prognosis due to older age, high copy number alterations, and frequent mutations in RUNX1, DNMT3A, and TP53 genes. Additionally, it showed higher proportions of cytotoxic cells and Tregs, suggesting potential sensitivity to mTOR inhibitors. CS1 had a better prognosis than CS2, with more copy number alterations, while CS2 had higher monocyte proportions. CS1 showed good sensitivity to cytarabine, while CS2 was sensitive to RXR agonists. Both CS1 and CS2, which predominantly featured mutations in FLT3, NPM1, and DNMT3A genes, benefited from FLT3 inhibitors. Using the Kappa test, our stratification model underwent robust validation in the miRNA and mRNA external validation datasets. With advancements in sequencing technology and machine learning algorithms, AML is poised to transition towards multi-omics precision medicine in the future. We aspire for our study to offer new perspectives on multi-drug combination clinical trials and multi-targeted precision medicine for AML.

Leprosy is a chronic infectious disease that mainly affects the skin and peripheral nerves, it can also invade deeper tissues and organs, including mucous membranes, lymph nodes, testes, eyes, and internal organs. Severe cases can result in deformities and disabilities. We encountered the case of a 39-year-old male with unexplained fever, headache and rash. The patient’s lesions were taken for histopathological examination and slit skin smear analysis. Further, the patient was detected of Mycobacterium leprae (M.leprae) nucleic acid sequences in the cerebrospinal fluid (CSF) and plasma, and M.leprae gene targets in the skin lesion tissue and blood. The patient was eventually diagnosed with multibacillary leprosy and type II leprosy reaction. These results suggest the possibility of bacteremia in patients with leprosy to some extent, and observation implies the potential invasion of CSF by M.leprae or its genetic material.

Deoxynivalenol (DON), commonly known as vomitoxin, is a mycotoxin produced by fungi and is frequently found as a contaminant in various cereal-based food worldwide. While the harmful effects of DON have been extensively studied in different tissues, its specific impact on the proliferation of skeletal muscle cells remains unclear. In this study, we utilized murine C2C12 myoblasts as a model to explore the influence of DON on their proliferation. Our observations indicated that DON exhibits dose-dependent toxicity, significantly inhibiting the proliferation of C2C12 cells. Through the application of RNA-seq analysis combined with gene set enrichment analysis, we identified a noteworthy downregulation of genes linked to the extracellular matrix (ECM) and condensed chromosome. Concurrently with the reduced expression of ECM genes, immunostaining analysis revealed notable changes in the distribution of fibronectin, a vital ECM component, condensing into clusters and punctate formations. Remarkably, the exposure to DON induced the formation of multipolar spindles, leading to the disruption of the normal cell cycle. This, in turn, activated the p53-p21 signaling pathway and ultimately resulted in apoptosis. These findings contribute significant insights into the mechanisms through which DON induces toxicity within skeletal muscle cells.

Abstract Background Mesenchymal stem/stromal cells (MSCs) have been acknowledged as the most important stromal cells in the bone marrow (BM) microenvironment for physiologic hematopoiesis and the concomitant hematologic malignancies. However, the systematic and detailed dissection of the biological and transcriptomic signatures of BM-MSCs in multiple myeloma (MM) are largely unknown. Methods In this study, we isolated and identified BM-MSCs from 10 primary MM patients and 10 healthy donors (HD). On the one hand, we compared the multifaceted biological characteristics of the indicated two BM-MSCs, including biomarker expression pattern, multilineage differentiation potential, stemness and karyotyping, together with the cellular vitality and immunosuppressive property. On the other hand, we took advantage of RNA-SEQ and bioinformatics analysis to verify the similarities and differences at the transcriptomic level between MM-MSCs and HD-MSCs. Results As to biological phenotypes and biofunctions, MM-MSCs revealed conservation in immunophenotype, stemness and differentiation towards adipocytes and chondrocytes with HD-MSCs, whereas with impaired osteogenic differentiation potential, cellular vitality and immunosuppressive property. As to transcriptomic properties, MM-MSCs revealed multidimensional alterations in gene expression profiling and genetic variations. Conclusions Overall, our date systematic and detailed reflected the multifaceted similarities and variations between MM-MSCs and HD-MSCs both at the cellular and molecular levels, and in particular, the alterations of immunomodulation and cellular viability of MM-MSCs, which wound benefit the further exploration of the pathogenesis and new drug application (NDA) of multiple myeloma from the view of BM-MSCs.

Abstract Continued emergence of SARS-CoV-2 variants of concern that are capable of escaping vaccine-induced immunity highlights the urgency of developing new COVID-19 therapeutics. An essential mechanism for SARS-CoV-2 infection begins with the viral spike protein binding to the human ACE2. Consequently, inhibiting this interaction becomes a highly promising therapeutic strategy against COVID-19. Herein, we demonstrate that ACE2-expressing human lung spheroid cells (LSC)-derived exosomes (LSC-Exo) could function as a prophylactic agent to bind and neutralize SARS-CoV-2, protecting the host against SARS-CoV-2 infection. Inhalation of LSC-Exo facilitates its deposition and biodistribution throughout the whole lung in a female mouse model. We show that LSC-Exo blocks the interaction of SARS-CoV-2 with host cells in vitro and in vivo by neutralizing the virus. LSC-Exo treatment protects hamsters from SARS-CoV-2-induced disease and reduced viral loads. Furthermore, LSC-Exo intercepts the entry of multiple SARS-CoV-2 variant pseudoviruses in female mice and shows comparable or equal potency against the wild-type strain, demonstrating that LSC-Exo may act as a broad-spectrum protectant against existing and emerging virus variants.

Abstract Background Abnormal blinking pattern is associated with ocular surface diseases. However, blink is difficult to analyze due to the rapid movement of eyelids. Deep learning machine (DLM) has been proposed as an optional tool for blinking analysis, but its clinical practicability still needs to be proven. Therefore, the study aims to compare the DLM-assisted Keratograph 5M (K5M) as a novel method with the currently available Lipiview in the clinic and assess whether blinking parameters can be applied in the diagnosis of dry eye disease (DED). Methods Thirty-five DED participants and 35 normal subjects were recruited in this cross-sectional study. DED questionnaire and ocular surface signs were evaluated. Blinking parameters including number of blinks, number of incomplete blinking (IB), and IB rate were collected from the blinking videos recorded by the K5M and Lipiview. Blinking parameters were individually collected from the DLM analyzed K5M videos and Lipiview generated results. The agreement and consistency of blinking parameters were compared between the two devices. The association of blinking parameters to DED symptoms and signs were evaluated via heatmap. Results In total, 140 eyes of 70 participants were included in this study. Lipiview presented a higher number of IB and IB rate than those from DLM-assisted K5M (P ≤ 0.006). DLM-assisted K5M captured significant differences in number of blinks, number of IB and IB rate between DED and normal subjects (P ≤ 0.035). In all three parameters, DLM-assisted K5M also showed a better consistency in repeated measurements than Lipiview with higher intraclass correlation coefficients (number of blinks: 0.841 versus 0.665; number of IB: 0.750 versus 0.564; IB rate: 0.633 versus 0.589). More correlations between blinking parameters and DED symptoms and signs were found by DLM-assisted K5M. Moreover, the receiver operating characteristic analysis showed the number of IB from K5M exhibiting the highest area under curve of 0.773. Conclusions DLM-assisted K5M is a useful tool to analyze blinking videos and detect abnormal blinking patterns, especially in distinguishing DED patients from normal subjects. Large sample investigations are therefore warranted to assess its clinical utility before implementation.

Blood composition is indicative of health-related traits such as immunity and metabolism. The use of molecular genetics to investigate alterations in these attributes in laying ducks is a novel approach. Our objective was to employ genome − wide association studies (GWAS) and haplotype − sharing analysis to identify genomic regions and potential genes associated with 11 blood components in Shaoxing ducks. Our findings revealed 35 SNPs and 1 SNP associated with low-density lipoprotein cholesterol (LDL) and globulin (GLB), respectively. We identified 36 putative candidate genes for the LDL trait in close proximity to major QTLs and key loci. Based on their biochemical and physiological properties, TRA2A, NPY, ARHGEF26, DHX36, and AADAC are the strongest putative candidate genes. Through linkage disequilibrium analysis and haplotype sharing analysis, we identified three haplotypes and one haplotype, respectively, that were significantly linked with LDL and GLB. These haplotypes could be selected as potential candidate haplotypes for molecular breeding of Shaoxing ducks. Additionally, we utilized a bootstrap test to verify the reliability of GWAS with small experimental samples. The test can be accessed at https://github.com/xuwenwu24/Bootstrap-test.

Photoaging, primarily caused by ultraviolet (UV) light, is the major factor in extrinsic skin aging. Existing anti-photoaging strategies mainly focus on early sun protection or repairing damaged skin, lacking a comprehensive treatment strategy. Therefore, this study developed a dressing that actively shields against UV radiation and repairs photoaged skin, offering double protection. This study utilized exosome-like nanovesicles derived from Olea europaea leaves (OLELNVs), enhancing them into a potent core biomaterial with high-dose effects and skin-friendly, non-cytotoxic inhibition of cell aging. These nanovesicles were incorporated into a cross-linked hyaluronic acid (HA) and tannic acid (TA) hydrogel with strong UV-absorbing properties, creating the OLELNVs@HA/TA hydrogel system. In vitro and in vivo experiments demonstrated that OLELNVs@HA/TA hydrogel can effectively reduce UV-induced skin damage and promote skin repair and regeneration. Additionally, RNA-seq and clustering analysis of miR168a-5p predicted targets revealed significant down-regulation of the NF-κB signaling pathway, mediating inflammatory aging responses. Overall, the OLELNVs@HA/TA hydrogel represents a novel dual-strategy approach for clinical application in combating photoaging.

Abstract RNA splicing dysregulation and the involvement of specific splicing factors are emerging as common factors in both obesity and metabolic disorders. The study provides compelling evidence that the absence of the splicing factor SRSF1 in mature adipocytes results in whitening of brown adipocyte tissue (BAT) and impaired thermogenesis, along with the inhibition of white adipose tissue browning in mice. Combining single‐nucleus RNA sequencing with transmission electron microscopy, it is observed that the transformation of BAT cell types is associated with dysfunctional mitochondria, and SRSF1 deficiency leads to degenerated and fragmented mitochondria within BAT. The results demonstrate that SRSF1 effectively binds to constitutive exon 6 of Ndufs3 pre‐mRNA and promotes its inclusion. Conversely, the deficiency of SRSF1 results in impaired splicing of Ndufs3, leading to reduced levels of functional proteins that are essential for mitochondrial complex I assembly and activity. Consequently, this deficiency disrupts mitochondrial integrity, ultimately compromising the thermogenic capacity of BAT. These findings illuminate a novel role for SRSF1 in influencing mitochondrial function and BAT thermogenesis through its regulation of Ndufs3 splicing within BAT.

BackgroundEsophageal cancer (EC) is a prevalent malignancy characterized by a low 5-year survival rate, primarily attributed to delayed diagnosis and limited therapeutic options. Currently, early detection of EC heavily relies on endoscopy and pathological examination, which pose challenges due to their invasiveness and high costs, leading to low patient compliance. The detection of DNA methylation offers a non-endoscopic, cost-effective, and secure approach that holds promising prospects for early EC detection.MethodsTo identify improved methylation markers for early EC detection, we conducted a comprehensive review of relevant literature, summarized the performance of DNA methylation markers based on different input samples and analytical methods in EC early detection and screening.FindingsThis review reveals that blood cell free DNA methylation-based method is an effective non-invasive method for early detection of EC, although there is still a need to improve its sensitivity and specificity. Another highly sensitive and specific non-endoscopic approach for early detection of EC is the esophageal exfoliated cells based-DNA methylation analysis. However, while there are substantial studies in esophageal adenocarcinoma, further more validation is required in esophageal squamous cell carcinoma.ConclusionIn conclusion, DNA methylation detection holds significant potential as an early detection and screening technology for EC.

High mobility group box 1 (HMGB1) is a nuclear DNA-binding protein with a dual role in cancer, acting as an oncogene and a tumor suppressor. This protein regulates nucleosomal structure, DNA damage repair, and genomic stability within the cell, while also playing a role in immune cell functions. This review comprehensively evaluates the biological and clinical significance of HMGB1 in cancer, including its involvement in cell death and survival, its potential as a therapeutic target and cancer biomarker, and as a prosurvival signal for the remaining cells after exposure to cytotoxic anticancer treatments. We highlight the need for a better understanding of the cellular markers and mechanisms involved in the involvement of HMGB1in cancer, and aim to provide a deeper understanding of its role in cancer progression.

Large quantity of observational data from ground and sounding meteorological observation data, ocean station observation data, ERA reanalysis data are used to count the sea fog process that occurred during April to July in Rizhao City from 1988 to 2019 altogether 32 years in this paper. The synoptic characteristics of the sea fog and their formation mechanism are statistically analyzed, and furthermore the main meteorological elements affecting the formation of sea fog in Rizhao area and their combined effects are put forward. The results indicate that sea fog occur in Rizhao area is most likely under the control of several weather conditions, such as the west of transition high to sea, the Pacific subtropical high ridge or the front of low or trough of the eastern China in spring and summer. Under the control of these synoptic characteristics, the direction and speed of wind, dew-point temperature, atmospheric temperature, SST, stratification stability of these hydrometeorological elements play an important role in the formation of sea fog. On these basis, the method of discriminance analysis is used to establish of discriminant equation for sea fog forecast. Through the forecast testing, the statistical forecasting method of sea fog has a great application, the forecast accuracy is between 88% and 94%. It can be used for short-term forecast of sea fog characteristics in Rizhao City, providing services for industry, agriculture, fishery production, sea and land transportation.

Three evident and meaningful characteristics of disruptive technology are the zeroing effect that causes sustaining technology useless for its remarkable and unprecedented progress, reshaping the landscape of technology and economy, and leading the future mainstream of technology system, all of which have profound impacts and positive influences. The identification of disruptive technology is a universally difficult task. Therefore, this paper aims to enhance the technical relevance of potential disruptive technology identification results and improve the granularity and effectiveness of potential disruptive technology identification topics. According to the life cycle theory, dividing the time stage, then constructing and analyzing the dynamic of technology networks to identify potential disruptive technology. Thereby, using the Latent Dirichlet Allocation (LDA) topic model further to clarify the topic content of potential disruptive technologies. This paper takes the large civil unmanned aerial vehicles (UAVs) as an example to prove the feasibility and effectiveness of the model. The results show that the potential disruptive technology in this field is the data acquisition, main equipment, and ground platform intelligence.

This study aimed to obtain a high yield and purity of Sargassum pallidum polyphenol extracts (SPPE) and study its enzyme activity. Fresh Sargassum pallidum seaweed was selected for optimization of ultrasound-assisted extraction (UAE) conditions and purification conditions using macroporous resin and Sephadex LH20 to obtain SPPE. The SPPE was characterized using UPLC-QTOF-MS/MS and α-amylase, α-glucosidase, tyrosinase, and AchE inhibitory activity were determined. The maximum extraction rate of SPPE was 7.56 mg GAE/g and the polyphenol purity reached 70.5% after macroporous resin and Sephadex LH-20 purification. A total of 50 compounds were identified by UPLC-QTOF-MS/MS. The IC50 values of SPPE were 334.9 μg/mL, 6.290 μg /mL, 0.834 mg /mL and 0.6538 mg /mL for α-amylase, α-glucosidase, tyrosinase and AchE, respectively. Molecular docking technology further revealed the effects of SPPE on the above enzymes. This study provided information on the potential hypoglycemic, whitening and anti-Alzheimer's disease biological activities of SPPE, which had guiding significance for the purification and development of other seaweed polyphenols.

It aimed to observe the effects of TongDu TiaoShen (TDTS) electroacupuncture (EA) on the analgesia and central system of knee osteoarthritis (KOA) rats and explore its mechanism. SD rats were rolled into the blank group, model group (KOA), control group (duloxetine 500 mg/kg/d, Ctrl), conventional EA group, and TDTS-EA group. Radiometric pain measurements and the Lequesne MG scale were used to evaluate the behavioral performance of the rats. Dopamine (DA), norepinephrine (NE), 5-hydroxytryptamine (5-HT), β-endorphin (β-EP), and leucine-enkephalin (L-ENK) were detected in the midbrain and spinal cord of lumbar enlargement. Interleukin (IL)-1β protein expression was detected by Western blot. The incubation period of thermal pain and foot contraction was decreased in the KOA group versus blank group, the Lequesne MG score was increased, DA, NE, 5-HT, β-EP, and L-ENK in the midbrain and spinal cord were increased, and synovial tissue IL-1β protein expression was increased (P

Abstract Real-time imaging of transient structure of the electronic excited state is fundamentally critical to understand and control ultrafast molecular dynamics. The ejection of electrons from the inner-shell and valence level can lead to the population of different excited states, which trigger manifold ultrafast relaxation processes, however, the accurate imaging of such electronic state-dependent structural evolutions is still lacking. Here, by developing the laser-induced electron recollision-assisted Coulomb explosion imaging approach and molecular dynamics simulations, snapshots of the vibrational wave-packets of the excited (A) and ground states (X) of D2O+ are captured simultaneously with sub-10 picometre and few-femtosecond precision. We visualise that θ DOD and ROD are significantly increased by around 50∘ and 10 pm, respectively, within approximately 8 fs after initial ionisation for the A state, and the ROD further extends 9 pm within 2 fs along the ground state of the dication in the present condition. Moreover, the ROD can stretch more than 50 pm within 5 fs along autoionisation state of dication. The accuracies of the results are limited by the simulations. These results provide comprehensive structural information for studying the fascinating molecular dynamics of water, and pave the way towards to make a movie of excited state-resolved ultrafast molecular dynamics and light-induced chemical reaction.

Abstract Background Appropriate medication is very important for pilots with acute stress disorder. Improper medication can not only affect the physical and mental health of the pilots but can also endanger flight safety. Hence, we aimed to quickly and effectively relieve symptoms and restore cognitive function by forming a consensus of Chinese experts on the pharmacological treatment of acute stress disorder in pilots using the Delphi method. Methods Relevant literature was searched to enumerate the current status of pharmacological treatment of acute stress disorder in pilots, followed by two rounds of expert consultation and discussion according to the listed status of the survey using the Delphi method. A descriptive statistical method was used to analyze the basic information, authority coefficients, concentration of opinions, and survey items of the experts to develop a consensus on the pharmacological treatment of acute stress disorder in pilots. Results A total of 16 experts in psychiatry, pharmacology, and aerospace medicine from different provinces and cities across China were invited for consultation. The recovery rate of the two rounds of consultation was 100%, and the expert authority coefficients were 0.897 and 0.906, respectively. Kendall’s coefficient of concordance of indicators at all levels was 0.564–0.594 (p

In order to determine the effect of different silicon window areas on the preservation of garlic in silicon windows, garlic was packed in polyethylene (PE) bags with an area of 30 cm×25 cm at low temperature in combination with 1, 3, 6 and 9 cm2 silicon window films, and a control group of polyethylene (PE) bags without silicon windows, and the quality indexes were measured within 120 d of storage. The results showed that the area of the silicon window had a greater influence on the weight loss, bud to cloves ratio and colour (ΔE) of the garlic after harvesting, and a smaller influence on the hardness and water content was observed. The optimal silicon window area was 6 cm2, the alliin content of garlic in the low temperature combined with 6 cm2 silicon window treatment group reached 0.38±0.00 g/100 g during 120 days of storage. Compared with 0 d, the alliin content increased by 50.97%, the malic acid content decreased by 92.38%, and the contents of citric acid, tartaric acid and fumaric acid increased by 21.13%, 65.87% and 43.26% respectively. The principal component analysis revealed that the key indicators of garlic freshness were ΔE value, weight loss, shoot to clove ratio, water content and tartaric acid content. Considering the variation of each index and the results of the principal component analysis, it was concluded that the use of 6 cm2 silicon window area combined with 30 cm×25 cm polyethylene (PE) bags at low temperature could effectively alleviate the deterioration of garlic storage quality. This study can provide a theoretical reference for the storage and processing of white-skinned garlic.

Abstract Background Patients with remitted major depressive disorder (rMDD) show abnormal functional connectivity of the central executive network (CEN), salience networks (SN) and default mode network (DMN). It is unclear how these change during remission, or whether changes are related to function. Methods Three spatial networks in 17 patients with rMDD were compared between baseline and the six-month follow-up, and to 22 healthy controls. Correlations between these changes and psychosocial functioning were also assessed. Results In the CEN, patients at baseline had abnormal functional connectivity in the right anterior cingulate, right dorsolateral prefrontal cortex (DLPFC) and inferior parietal lobule (IPL) compare with HCs. There were functional connection differences in the right DLPFC and left IPL at baseline during follow-up. Abnormal connectivity in the right DLPFC and medial prefrontal cortex (mPFC) were found at follow-up. In the SN, patients at baseline had abnormal functional connectivity in the insula, left anterior cingulate, left IPL, and right precuneus; compared with baseline, patients had higher connectivity in the right DLPFC at follow-up. In the DMN, patients at baseline had abnormal functional connectivity in the right mPFC. Resting-state functional connectivity of the IPL and DLPFC in the CEN correlated with psychosocial functioning. Conclusions At six-month follow-up, the CEN still showed abnormal functional connectivity in those with rMDD, while anomalies in the SN and DMN has disappeared. Resting-state functional connectivity of the CEN during early rMDD is associated with psychosocial function. Clinical trials Registration Pharmacotherapy and Psychotherapy for MDD after Remission on Psychology and Neuroimaging. https://www.clinicaltrials.gov/ , registration number: NCT01831440 (15/4/2013).

Abstract The interplay among symmetry of lattices, electronic correlations, and Berry phase of the Bloch states in solids has led to fascinating quantum phases of matter. A prototypical system is the magnetic Weyl candidate SrRuO3, where designing and creating electronic and topological properties on artificial lattice geometry is highly demanded yet remains elusive. Here, we establish an emergent trigonal structure of SrRuO3 by means of heteroepitaxial strain engineering along the [111] crystallographic axis. Distinctive from bulk, the trigonal SrRuO3 exhibits a peculiar XY-type ferromagnetic ground state, with the coexistence of high-mobility holes likely from linear Weyl bands and low-mobility electrons from normal quadratic bands as carriers. The presence of Weyl nodes are further corroborated by capturing intrinsic anomalous Hall effect, acting as momentum-space sources of Berry curvatures. The experimental observations are consistent with our first-principles calculations, shedding light on the detailed band topology of trigonal SrRuO3 with multiple pairs of Weyl nodes near the Fermi level. Our findings signify the essence of magnetism and Berry phase manipulation via lattice design and pave the way towards unveiling nontrivial correlated topological phenomena.

Abstract Neutral H2 formation via intramolecular hydrogen migration in hydrocarbon molecules plays a vital role in many chemical and biological processes. Here, employing cold target recoil ion momentum spectroscopy (COLTRIMS) and pump-probe technique, we find that the non-adiabatic coupling between the ground and excited ionic states of ethane through conical intersection leads to a significantly high yield of neutral H2 fragment. Based on the analysis of fingerprints that are sensitive to orbital symmetry and electronic state energies in the photoelectron momentum distributions, we tag the initial electronic population of both the ground and excited ionic states and determine the branching ratios of H2 formation channel from those two states. Incorporating theoretical simulation, we established the timescale of the H2 formation to be ~1300 fs. We provide a comprehensive characterization of H2 formation in ionic states of ethane mediated by conical intersection and reveals the significance of non-adiabatic coupling dynamics in the intramolecular hydrogen migration.

Noncoding RNAs (ncRNAs) are a class of nucleotide sequences that cannot be translated into peptides. ncRNAs can function post-transcriptionally by splicing complementary sequences of mRNAs or other ncRNAs or by directly engaging in protein interactions. Over the past few decades, the pervasiveness of ncRNAs in cell physiology and their pivotal roles in various diseases have been identified. One target regulated by ncRNAs is connexin (Cx), a protein that forms gap junctions and hemichannels and facilitates intercellular molecule exchange. The aberrant expression and misdistribution of connexins have been implicated in central nervous system diseases, cardiovascular diseases, bone diseases, and cancer. Current databases and technologies have enabled researchers to identify the direct or indirect relationships between ncRNAs and connexins, thereby elucidating their correlation with diseases. In this review, we selected the literature published in the past five years concerning disorders regulated by ncRNAs via corresponding connexins. Among it, microRNAs that regulate the expression of Cx43 play a crucial role in disease development and are predominantly reviewed. The distinctive perspective of the ncRNA–Cx axis interprets pathology in an epigenetic manner and is expected to motivate research for the development of biomarkers and therapeutics.

PIWI-interacting RNAs (piRNAs), a class of small non-coding RNAs (sncRNAs) with 24–32 nucleotides (nt), were initially identified in the reproductive system. Unlike microRNAs (miRNAs) or small interfering RNAs (siRNAs), piRNAs normally guide P-element-induced wimpy testis protein (PIWI) families to slice extensively complementary transposon transcripts without the seed pairing. Numerous studies have shown that piRNAs are abundantly expressed in the brain, and many of them are aberrantly regulated in central neural system (CNS) disorders. However, the role of piRNAs in the related developmental and pathological processes is unclear. The elucidation of piRNAs/PIWI would greatly improve the understanding of CNS development and ultimately lead to novel strategies to treat neural diseases. In this review, we summarized the relevant structure, properties, and databases of piRNAs and their functional roles in neural development and degenerative disorders. We hope that future studies of these piRNAs will facilitate the development of RNA-based therapeutics for CNS disorders.

Rice (Oryza sativa L.) is one of the primary sources of energy and nutrients needed by the body, and rice resistant starch (RRS) has been found to have hypoglycemic effects. However, its biological activity and specific mechanisms still need to be further elucidated. In the present study, 52 RRS differential metabolites were obtained from mouse liver, rat serum, canine feces, and human urine, and 246 potential targets were identified through a literature review and database analysis. A total of 151 common targets were identified by intersecting them with the targets of type 2 diabetes mellitus (T2DM). After network pharmacology analysis, 11 core metabolites were identified, including linolenic acid, chenodeoxycholic acid, ursodeoxycholic acid, deoxycholic acid, lithocholic acid, lithocholylglycine, glycoursodeoxycholic acid, phenylalanine, norepinephrine, cholic acid, and L-glutamic acid, and 16 core targets were identified, including MAPK3, MAPK1, EGFR, ESR1, PRKCA, FYN, LCK, DLG4, ITGB1, IL6, PTPN11, RARA, NR3C1, PTPN6, PPARA, and ITGAV. The core pathways included the neuroactive ligand–receptor interaction, cancer, and arachidonic acid metabolism pathways. The molecular docking results showed that bile acids such as glycoursodeoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, lithocholic acid, deoxycholic acid, and cholic acid exhibited strong docking effects with EGFR, ITGAV, ITGB1, MAPK3, NR3C1, α-glucosidase, and α-amylase. In vitro hypoglycemic experiments further suggested that bile acids showed significant inhibitory effects on α-glucosidase and α-amylase, with CDCA and UDCA having the most prominent inhibitory effect. In summary, this study reveals a possible hypoglycemic pathway of RRS metabolites and provides new research perspectives to further explore the therapeutic mechanism of bile acids in T2DM.

In this study, the main components of the extract of (Lithocarpus litseifolius folium extract, LLFE) were analyzed,and the anti-oxidative stress and anti-aging effects of LLFE on C.elegans were evaluated using Caenorhabditis elegans (C.elegans) as a model to explore the possible mechanisms of action.The results showed that LLFE contained 52.84±1.45 mg/g of total phenols, 380.74±15.12 mg/g of total flavonoids, 470.36±5.84 mg/g of total sugars and about 6.00% of dihydrochalcone compounds, with phloridzin 52.76±0.71 mg/g, phloretin 1.64±0.06 mg/g and trilobatin 4.88±0.01 mg/g. LLFE (0.25, 1.25 mg/mL) also significantly extended the mean lifespan of C.elegans under oxidative and heat stress conditions (P

Abstract Background To investigate the association between clinical periodontal parameters of periodontitis, serum lipid metabolism markers and adipokines’ levels in patients with obesity and periodontitis. Methods A total of 112 patients admitted to Hospital of Xi’an Jiaotong University were included in this study. They were divided into normal body weight group (18.5

In this study, non-targeted metabolomic research was conducted using gas chromatography-mass spectrometry (GC-MS) on Laba garlic at different storage times to explore the signature metabolite changes during storage. Multivariate statistical analysis was used to screen out the significant metabolites of Laba garlic at different storage times. Further, the deep learning support vector machine recursive feature elimination (SVM-RFE) algorithm was used to determine its landmark metabolites, and enrichment analysis of the pathways of its landmark metabolites was carried out. A total of 57 different metabolites were screened out (VIP≥1, P

Abstract Hematopoietic stem cells (HSCs) are the common and essential precursors of all blood cells, including immune cells, and they are responsible for the lifelong maintenance and damage repair of blood tissue homeostasis. The vast majority (> 95%) of HSCs are in a resting state under physiological conditions and are only activated to play a functional role under stress conditions. This resting state affects their long-term survival and is also closely related to the lifelong maintenance of hematopoietic function; however, abnormal changes may also be an important factor leading to the decline of immune function in the body and the occurrence of diseases in various systems. While the importance of resting HSCs has attracted increasing research attention, our current understanding of this topic remains insufficient, and the direction of clinical targeted treatments is unclear. Here, we describe the functions of HSCs, analyze the regulatory mechanisms that affect their resting state, and discuss the relationship between resting HSCs and different diseases, with a view to providing guidance for the future clinical implementation of related targeted treatments.

Abstract The Hammett equation is commonly used to theoretically depict the remote electronic effects of substituents on catalytic activities of metal nodes of metal-organic frameworks (MOFs). However, the application of the theory to MOF catalysts usually encounters problems because it relies heavily on empirical parameters with unknown transferability. To develop an alternative prediction theory, the linker orbital energy model has been proposed by density functional theory calculations. The model provides a simple method to approximately depict the remote electronic substituent effects on catalytic activities of metal nodes of MOFs, and its general applicability to MOFs is supported by extensively revisiting the structure-activity relationships reported in the literatures. The model can be used to design catalytic activity of metal nodes of MOFs by engineering the electronic properties of linkers and substituents.

Abstract Background Significant association between bullous pemphigoid (BP) and stroke has been reported. This study aimed to evaluate the level of anti-BP180 antibody in stroke patients to explore the relationship between BP and stroke in their pathogenesis. Methods We collected serum samples from stroke patients and matched controls between February 2019 and June 2020. The anti-BP180 antibody levels were measured by enzyme-linked immunosorbent assay (ELISA). Results A total of 1183 stroke patients including 970 with cerebral infarction (CI), 192 with intracerebral hemorrhage (ICH), 21 with CI and ICH, and 855 controls were enrolled in this study. Anti-BP180 autoantibody values were significantly higher in stroke patients than in controls (p < 0.001). Anti-BP180 autoantibody-positive rates were 12.51% (148) in stroke patients and 4.68% (40) in controls (p < 0.001, OR = 2.65). In anti-BP180 autoantibody-positive subjects, the values were significantly higher in stroke patients than in controls (p < 0.001). However, only 10 (6.76%) stroke patients and 3 (7.5%) controls had high values (> 100 RU/mL) (p = 0.87). Stratified analysis showed that anti-BP180 antibody positive rates were independent of age, sex, and stroke subtypes in the stroke group. Positive rates in patients with both CI and ICH were nearly two times higher than those in patients with either CI or ICH alone (p = 0.11, OR = 1.94). Study limitations This study had a limited sample size and lacked quantitative criteria for stroke severity. Conclusions Anti-BP180 antibody values and positive rates were higher in stroke patients than in controls, suggesting that stroke patients may have higher of developing BP.

Abstract To date, genome‐wide association studies (GWASs) have discovered 35 susceptible loci of leprosy; however, the cumulative effects of these loci can only partially explain the overall risk of leprosy, and the causal variants and genes within these loci remain unknown. Here, we conducted out new GWASs in two independent cohorts of 5007 cases and 4579 controls and then a meta‐analysis in these newly generated and multiple previously published (2277 cases and 3159 controls) datasets were performed. Three novel and 15 previously reported risk loci were identified from these datasets, increasing the known leprosy risk loci of explained genetic heritability from 23.0 to 38.5%. A comprehensive fine‐mapping analysis was conducted, and 19 causal variants and 14 causal genes were identified. Specifically, manual checking of epigenomic information from the Epimap database revealed that the causal variants were mainly located within the immune‐relevant or immune‐specific regulatory elements. Furthermore, by using gene‐set, tissue, and cell‐type enrichment analyses, we highlighted the key roles of immune‐related tissues and cells and implicated the PD‐1 signaling pathways in the pathogenetic mechanism of leprosy. Collectively, our study identified candidate causal variants and elucidated the potential regulatory and coding mechanisms for genes associated with leprosy.

ABSTRACTWe designed and developed a novel DNA topoisomerase I inhibitor MF-6, which was a more potent cytotoxin and a more potent inducer of immunogenic cell death compared with DXd. To utilize MF-6’s ability to induce antitumor immunity, a human epidermal growth factor receptor 2 (HER2)-targeted antibody–drug conjugate (ADC) trastuzumab-L6 that included a cleavable linker and MF-6 was developed. Different from traditional cytotoxic ADC, the antitumor activity of trastuzumab-L6 was assessed by inducing tumor cell immunogenic cell death, activating dendritic cells and cytotoxic CD8+ T cells to acquire durable adaptive immune memory. Tumor cells treated with trastuzumab-L6 were committed to immunogenic cell death, with upregulation of damage-associated molecular patterns and antigen presentation molecules. In a syngeneic tumor model with a mouse cell line that expressed human HER2, immunocompetent mice showed greater antitumor efficacy compared with nude mice. The trastuzumab-L6-cured immunocompetent mice acquired adaptive antitumor memory and rejected subsequent tumor cell challenge. The trastuzumab-L6 efficacy was abrogated when cytotoxic CD8+ T cells were depleted and enhanced when regulatory CD4+ T cells were depleted. The combination of trastuzumab-L6 with immune checkpoint inhibitors significantly increased antitumor efficacy. Enhanced T cell infiltration, dendritic cell activation, and decreased type M2 macrophages in tumor post trastuzumab-L6 administration confirmed the immune-activating responses. In conclusion, trastuzumab-L6 was considered to be an immunostimulatory agent, rather than a traditional cytotoxic ADC, and its antitumor efficacy was enhanced when combined with an anti-PD-L1 and anti-CTLA-4 antibody, which suggested a potential therapeutic strategy.

Abstract Complete regeneration of damaged tissues/organs has always been the ultimate challenge in regenerative medicine. Aging has long been considered the basis of age‐related diseases, as senescent cells gradually accumulate in tissues with increasing age, tissues exhibit aging and normal physiological functions are inhibited. In recent years, in damaged tissues, scholars have found that the number of cells with features of cellular senescence continues to increase over time. The accumulation of senescent cells severely hinders the healing of damaged tissues. Furthermore, by clearing senescent cells or inhibiting the aging microenvironment, damaged tissues regained their original regenerative and repair capabilities. On the other hand, various biomaterials have been proved to have good biocompatibility and can effectively support cell regeneration after injury. Combining the two solutions, inhibiting the cellular senescence in damaged tissues and establishing a pro‐regenerative environment through biomaterial technology gradually reveals a new, unexpected treatment strategy applied to the field of regenerative medicine. In this review, we first elucidate the main characteristics of senescent cells from morphological, functional and molecular levels, and discuss in detail the process of accumulation of senescent cells in tissues. Then, we will explore in depth how the accumulation of senescent cells after damage affects tissue repair and regeneration at different stages. Finally, we will turn to how to promote tissue regeneration and repair in the field of regenerative medicine by inhibiting cellular senescence combined with biomaterial technology. Our goal is to understand the relationship between cellular senescence and tissue regeneration through this new perspective, and provide valuable references for the development of new therapeutic strategies in the future.

Although bivalirudin has been recently made available for purchase in China, large-scale analyses on the safety profile of bivalirudin among Chinese patients is lacking. Thus, this study aimed to compare the safety profile of bivalirudin and heparin as anticoagulants in Chinese ST-segment elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). A total of 1063 STEMI patients undergoing PCI and receiving bivalirudin (n=424, bivalirudin group) or heparin (n=639, heparin group) as anticoagulants were retrospectively enrolled. The net adverse clinical events (NACEs) within 30 days after PCI were recorded, including major adverse cardiac and cerebral events (MACCEs) and bleeding events (bleeding academic research consortium (BARC) grades 2-5 (BARC 2-5)). The incidences of NACEs (10.1 vs 15.6%) (P=0.010), BARC 2-5 bleeding events (5.2 vs 10.3%) (P=0.003), and BARC grades 3-5 (BARC 3-5) bleeding events (2.1 vs 5.5%) (P=0.007) were lower in the bivalirudin group compared to the heparin group, whereas general MACCEs incidence (8.9 vs 6.4%) (P=0.131) and each category of MACCEs (all P>0.05) did not differ between two groups. Furthermore, the multivariate logistic analyses showed that bivalirudin (vs heparin) was independently correlated with lower risk of NACEs (OR=0.508, P=0.002), BARC 2-5 bleeding events (OR=0.403, P=0.001), and BARC 3-5 bleeding events (OR=0.452, P=0.042); other independent risk factors for NACEs, MACCEs, or BARC bleeding events included history of diabetes mellitus, emergency operation, multiple lesional vessels, stent length >33.0 mm, and higher CRUSADE score (all P

Hypericin is widely utilized for its precise antidepressant properties, but its exact antidepressant mechanism remains unclear. Gap junctions, which were predominantly expressed in astrocytes in the central nervous system, are concerned with the pathogenesis of depression. However, the role of hypericin in gap junctional dysfunction in depression has rarely been investigated. Here, we found that gap junctions were ultra-structurally broadened in the chronic unpredictable stress (CUS) rat model of depression, while hypericin repaired the dysfunction of gap junctions. Suppression of gap junctions by bilateral injection of carbenoxolone (CBX) in the prefrontal cortex of rats significantly inhibited the restoration of gap junctional dysfunction in depression by hypericin. Meanwhile, hypericin failed to show antidepressant benefits. Furthermore, in corticosterone (CORT)-stimulated primary astrocytes derived from neonatal rats, hypericin dramatically reversed the phosphorylation of connexin 43 (Cx43), normalizing the expression of Cx43 and thereby ameliorating gap junctional dysfunction. Comparatively, CBX inhibited the remission of hypericin on gap junctional intercellular communication function. Gap junctional function might be a novel therapeutic target for hypericin in the treatment of depression and provide potential novel insights into the antidepressant mechanism of other herbal ingredients.

Background: Osteoporosis is a significant barrier to the use of dental implants in the elderly for the treatment of tooth defects. Adipose derived stem cells (ADSCs) have demonstrated extensive potential for tissue repair and regeneration. The present study aimed to investigate the effectiveness of ADSCs engineered to express high levels of osteoprotegerin (OPG) for the treatment of bone loss in implant dentistry caused by estrogen deficiency. Methods: A rat model of osteoporosis was established through double oophorectomy, and the rats were treated by gene modified cells Adv-OPG-ADSCs. The effects of the treatment on maxilla tissue changes were evaluated using HE staining and micro-CT. Additionally, ALP and TRAP staining were used to assess osteoblast and osteoclast alterations. Finally, the changes in related osteoblast and osteoclast indicators were measured by RT-qPCR, Western blot, and ELISA. Results: The successfully generated high-OPG-expressing ADSCs led to increase of cell viability, proliferation, and osteoblast differentiation. Treatment with Adv-OPG-ADSCs significantly ameliorated maxillary morphology, trabecular volume reduction, and bone mineral density decline in the model of estrogen-deficient maxillary implant dentistry. Furthermore, the treatment was beneficial to promoting the generation of osteoblasts and inhibiting the generation of osteoclast. Adv-OPG-ADSCs increased OPG, ALP, OCN, and Runx-2 expressions in the maxilla while suppressing RANKL expression, and also increased the concentration of COL I and PINP, as well as decreased the concentration of CTX-1. Conclusion: Adv-OPG-ADSCs promote the formation of osteoblasts and inhibit the generation of osteoclasts, thereby inhibiting bone absorption, facilitating bone formation, and promoting the repair of maxillary bone after dental implantation in the presence of osteoporosis-related complications, especially in the setting of estrogen deficiency, providing scientific basis for the application of Adv-OPG-ADSCs in the treatment of implant related osteoporosis.

In order to increase the sensory evaluation score of bottling fermentation draft Huangjiu indicated by the national judges and young students, six factors of the fermentation (initial brix, water bath sterilization time, liquid filling amount, fermentation temperature, fermentation time, inoculation amount) were analyzed by Plackett-Burman tests in which three significant factors were screened as initial brix, fermentation temperature and time. Then the reasonable range of factors was determined by the steepest ascent method, and optimized by central composite design response surface test. The model was significant and therefore provided a good fit to the actual data and predicted responses. The results showed that the optimal initial brix, fermentation time, temperature, filling volume, 95 ℃ water bath and inoculum volume were 126 g/L, 20.5 ℃, 69.2 h , 195 mL, 2.5 h, 10 mL, respectively. Under the optimal conditions, the sensory evaluation score of bottling fermentation draft Huangjiu reached 96.6, which was better than that before tests.

The chemical composition and nutritional content of garlic are greatly impacted by its production location, leading to distinct flavor profiles and functional properties among garlic varieties from diverse origins. Consequently, these variations determine the preference and acceptance among diverse consumer groups. In this study, purple-skinned garlic samples were collected from five regions in China: Yunnan, Shandong, Henan, Anhui, and Jiangsu Provinces. Mid-infrared spectroscopy and ultraviolet spectroscopy were utilized to analyze the components of garlic cells. Three preprocessing methods, including Multiple Scattering Correction (MSC), Savitzky–Golay Smoothing (SG Smoothing), and Standard Normalized Variate (SNV), were applied to reduce the background noise of spectroscopy data. Following variable feature extraction by Genetic Algorithm (GA), a variety of machine learning algorithms, including XGboost, Support Vector Classification (SVC), Random Forest (RF), and Artificial Neural Network (ANN), were used according to the fusion of spectral data to obtain the best processing results. The results showed that the best-performing model for ultraviolet spectroscopy data was SNV-GA-ANN, with an accuracy of 99.73%. The best-performing model for mid-infrared spectroscopy data was SNV-GA-RF, with an accuracy of 97.34%. After the fusion of ultraviolet and mid-infrared spectroscopy data, the SNV-GA-SVC, SNV-GA-RF, SNV-GA-ANN, and SNV-GA-XGboost models achieved 100% accuracy in both training and test sets. Although there were some differences in the accuracy of the four models under different preprocessing methods, the fusion of ultraviolet and mid-infrared spectroscopy data yielded the best outcomes, with an accuracy of 100%. Overall, the combination of ultraviolet and mid-infrared spectroscopy data fusion and chemometrics established in this study provides a theoretical foundation for identifying the origin of garlic, as well as that of other agricultural products.

The effects of the roasting-assisted aqueous ethanol extraction of peanut oil on the structure and functional properties of dreg proteins were investigated to interpret the high free oil yield and provide a basis for the full utilization of peanut protein resources. The roasting-assisted aqueous ethanol extraction of peanut oil obtained a free oil yield of 97.74% and a protein retention rate of 75.80% in the dreg. The water-holding capacity of dreg proteins increased significantly, and the oil-holding capacity and surface hydrophobicity decreased significantly, reducing the binding ability with oil and thus facilitating the release of oil. Although the relative crystallinity and denaturation enthalpy of the dreg proteins decreased slightly, the denaturation temperatures remained unchanged. Infrared and Raman spectra identified decreases in the C-H stretching vibration, Fermi resonance and α-helix, and increases in random coil, β-sheet and β-turn, showing a slight decrease in the overall ordering of proteins. After the roasting treatment, 62.57–135.33% of the protein functional properties were still preserved. Therefore, the roasting-assisted aqueous ethanol extraction of peanut oil is beneficial for fully utilizing the oil and protein resources in peanuts.

In this study, gas chromatography-mass spectrometry (GC-MS) based untargeted metabolomics was used to describe the changes of metabolites in edible grass with Lactobacillus plantarum (Lp) fermentation durations of 0 and 7 days, and subsequently to investigate the protective effect of fermented edible grass on acetaminophen-induced stress injury in HepG2 cells. Results showed that 53 differential metabolites were identified, including 31 significantly increased and 22 significantly decreased metabolites in fermented edible grass. Fermented edible grass protected HepG2 cells against acetaminophen-induced stress injury, which profited from the reduction in lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels and the enhancement in superoxide dismutase (SOD) activity. Cell metabolomics analysis revealed that a total of 13 intracellular and 20 extracellular differential metabolites were detected. Fermented edible grass could regulate multiple cell metabolic pathways to exhibit protective effects on HepG2 cells. These findings provided theoretical guidance for the formation and regulation of bioactive metabolites in fermented edible grass and preliminarily confirmed the protective effects of fermented edible grass on drug-induced liver damage.

Background: Gestational hypertension and pre-eclampsia often increase maternal and neonatal mortality. The illness usually appears after the 20th week of pregnancy due to malnutrition or obesity. Untreated, it can lead to neonatal and maternal mortality. Low-dose Aspirin can prevent preeclampsia if started between 11 and 28 weeks. Several studies support this technique, although others have shown limited effectiveness and negative side effects. Objective: This study aims to assess the effectiveness of aspirin treatment for the prevention of preeclampsia, taking into account any possible adverse reactions. Methods: This observational research comprised 600 singleton pregnant women at high risk of pregnancy-induced hypertension. The aspirin group had 301 individuals and the placebo group 299. From 11 to 36 weeks of pregnancy, they received 150 mg of aspirin and 150 mg of placebo. Gestational hypertension was assessed at 25 weeks, 36 weeks, and 37 weeks. If any, aspirin and placebo-related adverse pregnancy and neonatal outcomes were reported. Results: With aspirin therapy, 4 females and 14 females with placebo developed gestational hypertension before 25 weeks of pregnancy with an odds ratio of 0.283 (0.092–0.87); before 36 weeks, 5 females and 15 females with placebo developed GHD with an odds ratio of 0.331 (0.118–0.922); and after 37 weeks, 17 females and 35 females with placebo developed GHD. Preeclampsia occurred in 5 females in the aspirin group and 17 in the placebo group at 37 weeks (odds ratio 0.5349 (0.307–0.930). Conclusion: In pregnant women at high risk of prenatal hypertension and preeclampsia, aspirin therapy is very effective with minimal side effects.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. Zinc oxide (ZnO) nanoparticles have excellent anti-tumor properties in the biomedical field. The present study aimed to explore the underlying mechanism by which ZnO nanoparticles induce toxicity in DLBCL cells (U2932) via the PINK1/Parkin-mediated mitophagy pathway. After U2932 cells were exposed to various concentrations of ZnO nanoparticles, the cell survival rate, reactive oxygen species (ROS) generation, cell cycle arrest, and changes in the expression of PINK1, Parkin, P62, and LC3 were monitored. Moreover, we investigated monodansylcadaverine (MDC) fluorescence intensity and autophagosome and further validated the results using the autophagy inhibitor 3-methyladenine (3-MA). The results showed that ZnO nanoparticles could effectively inhibit the proliferation of U2932 cells and induce cell cycle arrest at the G0/G1 phases. Moreover, ZnO nanoparticles significantly increased ROS production, MDC fluorescence intensity, autophagosome formation, and the expression of PINK1, Parkin, and LC3, and decreased the expression of P62 in U2932 cells. In contrast, the autophagy level was reduced after the intervention of the 3-MA. Overall, ZnO nanoparticles can trigger PINK1/Parkin-mediated mitophagy signaling in U2932 cells, which may be a potential therapeutic approach for DLBCL.

BackgroundM. leprae preferentially infects Schwann cells (SCs) in the peripheral nerves leading to nerve damage and irreversible disability. Knowledge of how M. leprae infects and interacts with host SCs is essential for understanding mechanisms of nerve damage and revealing potential new therapeutic strategies.Methodology/principal findingsWe performed a time-course single-cell sequencing analysis of SCs infected with M. leprae at different time points, further analyzed the heterogeneity of SCs, subpopulations associated with M. leprae infection, developmental trajectory of SCs and validated by Western blot or flow cytometry. Different subpopulations of SCs exhibiting distinct genetic features and functional enrichments were present. We observed two subpopulations associated with M. leprae infection, a stem cell-like cell subpopulation increased significantly at 24 h but declined by 72 h after M. leprae infection, and an adipocyte-like cell subpopulation, emerged at 72 h post-infection. The results were validated and confirmed that a stem cell-like cell subpopulation was in the early stage of differentiation and could differentiate into an adipocyte-like cell subpopulation.Conclusions/significanceOur results present a systematic time-course analysis of SC heterogeneity after infection by M. leprae at single-cell resolution, provide valuable information to understand the critical biological processes underlying reprogramming and lipid metabolism during M. leprae infection of SCs, and increase understanding of the disease-causing mechanisms at play in leprosy patients as well as revealing potential new therapeutic strategies.