Population-level exploration of alternative splicing and its unique role in controlling agronomic traits of rice.

Alternative splicing (AS) plays crucial roles in regulating various biological processes in plants. However, the genetic mechanisms underlying AS and its role in controlling important agronomic traits in rice (Oryza sativa) remain poorly understood. In this study, we explored AS in rice leaves and panicles using the rice minicore collection. Our analysis revealed a high level of transcript isoform diversity, with approximately one fifth of potential isoforms acting as major transcripts in both tissues. Regarding the genetic mechanism of AS, we found that the splicing of 833 genes in the leaf and 1,230 genes in the panicle was affected by cis-genetic variation. Twenty-one percent of these AS events could only be explained by large structural variations. Approximately 77.5% of genes with significant splicing quantitative trait loci (sGenes) exhibited tissue-specific regulation, and AS can cause 26.9% (leaf) and 23.6% (panicle) of sGenes to have altered, lost or gained functional domains. Additionally, through splicing-phenotype association analysis, we identified phosphate-starvation induced RING-type E3 ligase (OsPIE1; LOC_Os01g72480), whose splicing ratio was significantly associated with plant height. In summary, this study provides an understanding of AS in rice and its contribution to the regulation of important agronomic traits.

Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins.

The current outbreak of coronavirus disease-2019 (COVID-19) poses unprecedented challenges to global health1. The new coronavirus responsible for this outbreak-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-shares high sequence identity to SARS-CoV and a bat coronavirus, RaTG132. Although bats may be the reservoir host for a variety of coronaviruses3,4, it remains unknown whether SARS-CoV-2 has additional host species. Here we show that a coronavirus, which we name pangolin-CoV, isolated from a Malayan pangolin has 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S proteins, respectively. In particular, the receptor-binding domain of the S protein of pangolin-CoV is almost identical to that of SARS-CoV-2, with one difference in a noncritical amino acid. Our comparative genomic analysis suggests that SARS-CoV-2 may have originated in the recombination of a virus similar to pangolin-CoV with one similar to RaTG13. Pangolin-CoV was detected in 17 out of the 25 Malayan pangolins that we analysed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus from pangolins that is closely related to SARS-CoV-2 suggests that these animals have the potential to act as an intermediate host of SARS-CoV-2. This newly identified coronavirus from pangolins-the most-trafficked mammal in the illegal wildlife trade-could represent a future threat to public health if wildlife trade is not effectively controlled.

Pathogenicity, tissue tropism and potential vertical transmission of SARSr-CoV-2 in Malayan pangolins.

Malayan pangolin SARS-CoV-2-related coronavirus (SARSr-CoV-2) is closely related to SARS-CoV-2. However, little is known about its pathogenicity in pangolins. Using CT scans we show that SARSr-CoV-2 positive Malayan pangolins are characterized by bilateral ground-glass opacities in lungs in a similar manner to COVID-19 patients. Histological examination and blood gas tests are indicative of dyspnea. SARSr-CoV-2 infected multiple organs in pangolins, with the lungs the major target, and histological expression data revealed that ACE2 and TMPRSS2 were co-expressed with viral RNA. Transcriptome analysis indicated that virus-positive pangolins were likely to have inadequate interferon responses, with relative greater cytokine and chemokine activity in the lung and spleen. Notably, both viral RNA and viral proteins were detected in three pangolin fetuses, providing initial evidence for vertical virus transmission. In sum, our study outlines the biological framework of SARSr-CoV-2 in pangolins, revealing striking similarities to COVID-19 in humans.

mRNA cleavage by 21-nucleotide phasiRNAs determines temperature-sensitive male sterility in rice.

Temperature-sensitive male sterility is one of the core components for hybrid rice (Oryza sativa) breeding based on the 2-line system. We previously found that knockout of ARGONAUTE 1d (AGO1d) causes temperature-sensitive male sterility in rice by influencing phased small interfering RNA (phasiRNA) biogenesis and function. However, the specific phasiRNAs and their targets underlying the temperature-sensitive male sterility in the ago1d mutant remain unknown. Here, we demonstrate that the ago1d mutant displays normal female fertility but complete male sterility at low temperature. Through a multiomics analysis of small RNA (sRNA), degradome, and transcriptome, we found that 21-nt phasiRNAs account for the greatest proportion of the 21-nt sRNA species in rice anthers and are sensitive to low temperature and markedly downregulated in the ago1d mutant. Moreover, we found that 21-nt phasiRNAs are essential for the mRNA cleavage of a set of fertility- and cold tolerance-associated genes, such as Earlier Degraded Tapetum 1 (EDT1), Tapetum Degeneration Retardation (TDR), OsPCF5, and OsTCP21, directly or indirectly determined by AGO1d-mediated gene silencing. The loss of function of 21-nt phasiRNAs can result in upregulation of their targets and causes varying degrees of defects in male fertility and grain setting. Our results highlight the essential functions of 21-nt phasiRNAs in temperature-sensitive male sterility in rice and suggest their promising application in 2-line hybrid rice breeding in the future.

A rice variation map derived from 10 548 rice accessions reveals the importance of rare variants.

Detailed knowledge of the genetic variations in diverse crop populations forms the basis for genetic crop improvement and gene functional studies. In the present study, we analyzed a large rice population with a total of 10 548 accessions to construct a rice super-population variation map (RSPVM), consisting of 54 378 986 single nucleotide polymorphisms, 11 119 947 insertion/deletion mutations and 184 736 presence/absence variations. Assessment of variation detection efficiency for different population sizes revealed a sharp increase of all types of variation as the population size increased and a gradual saturation of that after the population size reached 10 000. Variant frequency analysis indicated that ∼90% of the obtained variants were rare, and would therefore likely be difficult to detect in a relatively small population. Among the rare variants, only 2.7% were predicted to be deleterious. Population structure, genetic diversity and gene functional polymorphism of this large population were evaluated based on different subsets of RSPVM, demonstrating the great potential of RSPVM for use in downstream applications. Our study provides both a rich genetic basis for understanding natural rice variations and a powerful tool for exploiting great potential of rare variants in future rice research, including population genetics and functional genomics.

A novel HMGA2::KITLG fusion in a dedifferentiated liposarcoma with amplification of MDM2 and HMGA2.

High-mobility group AT-hook 2 (HMGA2) is rearranged in various types of mesenchymal tumors, particularly lipomas. HMGA2 is also co-amplified with mouse double minute 2 (MDM2) in well-differentiated liposarcoma/dedifferentiated liposarcoma (WDLPS/DDLPS). We report a case of relapsed DDLPS with a novel in-frame fusion between HMGA2 and KITLG, which encodes the ligand for KIT kinase, a critical protein involved in gametogenesis, hematopoiesis, and melanogenesis. The HMGA2 breakpoint is in intron 3, a commonly observed location for HMGA2 rearrangements, while the KITLG breakpoint is in intron 2, leading to a fusion protein that contains almost the entire coding sequence of KITLG. By immunohistochemical staining, tumor cells expressed KIT and showed phosphorylated MAPK, a major KIT downstream target. We suggest an oncogenic mechanism that involves the overexpression of KITLG caused by its rearrangement with HMGA2, leading to the constitutive activation of KIT kinase. While MDM2 amplification was observed in both the primary tumor and the relapsed tumor, the HMGA2::KITLG was only present in the relapsed tumor, indicating the role of HMGA2::KITLG in disease progression.

Hydrogen Bonding-Induced Aggregation of Chiral Functionalized AuNS@Ag NPs for Photothermal Enantioanalysis.

Toward the challenges of signaling transduction amplified in enantioselective recognition, we herein devised an innovative strategy for highly selective recognition of amino acids and their derivatives, leveraging photothermal effects. In this approach, bifunctional l-ascorbic acid is employed to reduce silver ions in situ on Au nanostars. Simultaneously, its oxidate (l-dehydroascorbic acid) is bonded to the silver shell as a chiral selector to prepare chiral nanoparticles (C-AuNS@Ag NPs) with the ability to recognize stereoisomers and sensitively modulate the photothermal effect. l-Dehydroascorbic acid can selectively capture one of the enantiomers of the two forms through hydrogen bonding and drive aggregation of the nanoparticles, which sharply enhances the photothermal effect. Consequently, the two forms of the system exhibit a significant temperature difference, which enables the discrimination and quantification of enantiomers. Our strategy verifies that six chiral amino acids and their derivatives can be discriminated with enantioselective response values of up to 79. Additionally, the chiral recognition mechanism was revealed through density functional theory (DFT) calculations, providing a paradigm shift in the development of enantiomeric recognition strategies.

Acclimation of intertidal macroalgae Ulva prolifera to UVB radiation: the important role of alternative oxidase.

BACKGROUND: Solar radiation is primarily composed of ultraviolet radiation (UVR, 200 - 400 nm) and photosynthetically active radiation (PAR, 400 - 700 nm). Ultraviolet-B (UVB) radiation accounts for only a small proportion of sunlight, and it is the primary cause of plant photodamage. The use of chlorofluorocarbons (CFCs) as refrigerants caused serious ozone depletion in the 1980s, and this had led to an increase in UVB. Although CFC emissions have significantly decreased in recent years, UVB radiation still remains at a high intensity. UVB radiation increase is an important factor that influences plant physiological processes. Ulva prolifera, a type of macroalga found in the intertidal zone, is intermittently exposed to UVB. Alternative oxidase (AOX) plays an important role in plants under stresses. This research examines the changes in AOX activity and the relationships among AOX, photosynthesis, and reactive oxygen species (ROS) homeostasis in U. prolifera under changes in UVB and photosynthetically active radiation (PAR). RESULTS: UVB was the main component of solar radiation impacting the typical intertidal green macroalgae U. prolifera. AOX was found to be important during the process of photosynthesis optimization of U. prolifera due to a synergistic effect with non-photochemical quenching (NPQ) under UVB radiation. AOX and glycolate oxidase (GO) worked together to achieve NADPH homeostasis to achieve photosynthesis optimization under changes in PAR + UVB. The synergism of AOX with superoxide dismutase (SOD) and catalase (CAT) was important during the process of ROS homeostasis under PAR + UVB. CONCLUSIONS: AOX plays an important role in the process of photosynthesis optimization and ROS homeostasis in U. prolifera under UVB radiation. This study provides further insights into the response of intertidal macroalgae to solar light changes.

Risk analysis of the association between different hemoglobin glycation index and poor prognosis in critical patients with coronary heart disease-A study based on the MIMIC-IV database.

BACKGROUND: The hemoglobin glycation index (HGI) is the difference between the observed and predicted values of glycosylated hemoglobin (HbA1c), which is closely associated with a variety of poor prognoses. However, there are still no studies on the correlation between HGI and poor prognosis in patients with critical coronary artery disease. The purpose of this study was to analyze the correlation between HGI and all-cause mortality in patients with critical coronary artery disease using the MIMIC-IV database. METHODS: The HGI was calculated by constructing a linear regression equation between HbA1c and fasting plasma glucose (FPG). A Kaplan‒Meier survival analysis model was constructed based on the HGI quartiles to clarify the differences in all-cause mortality rates between groups, and the log-rank test was used to assess the differences between groups. The hazard ratio (HR) of HGI as a risk factor for outcome events was assessed using the Cox proportional risk model and restricted cubic spline (RCS), with the Q2 group serving as the reference group. RESULTS: A total of 5260 patients were included in this study. The 30-day mortality rate of the patients was 4.94% and the mortality rate within 365 days was 13.12%. A low HGI was significantly associated with 30-day mortality (HR, 1.96; 95% CI, (1.38, 2.78); P < 0.001) and 365-day mortality (HR, 1.48; 95% CI, (1.19, 1.85); P < 0.001) in patients with critical coronary artery disease in the completely adjusted Cox proportional risk model. In addition, high levels of HGI were associated with 365-day mortality (HR, 1.31; 95% CI, (1.02, 1.69); P < 0.05). RCS analysis revealed a U-shaped relationship between HGI and outcome events. According to the stratified analysis, the interaction test revealed that the correlation between HGI and outcome events remained stable. CONCLUSION: There was a significant correlation between HGI and all-cause mortality in patients with critical coronary artery disease, particularly in those with low HGI. HGI can be used as a potential indicator for assessing the short- and long-term risk of mortality in such patients.

IR808@MnO nano-near infrared fluorescent dye's diagnostic value for malignant pleural effusion.

BACKGROUND: Malignant pleural effusion is mostly a complication of advanced malignant tumors. However, the cancer markers such as carbohydrate antigen 125 (CA 125), carbohydrate antigen 15-3 (CA 15-3), carbohydrate antigen 19-9 (CA 19-9), and cytokeratin fragment 21-1 (CYFRA 21-1) have low sensitivity and organ specificity for detecting malignant pleural effusion. RESEARCH QUESTION: Is IR808@MnO nano-near infrared fluorescent dye worthy for the diagnosis in differentiating benign and malignant pleural effusions. STUDY DESIGN AND METHODS: This experiment was carried out to design and characterize the materials for in vitro validation of the new dye in malignant tumor cells in the A549 cell line and in patients with adenocarcinoma pleural effusion. The dye was verified to possess tumor- specific targeting capabilities. Subsequently, a prospective hospital-based observational study was conducted, enrolling 106 patients and excluding 28 patients with unknown diagnoses. All patients underwent histopathological analysis of thoracoscopic biopsies, exfoliative cytological analysis of pleural fluid, and analysis involving the new dye. Statistical analyses were performed using Microsoft Excel, GraphPad Prism, and the R language. RESULTS: The size of IR808@MnO was 136.8 ± 2.9 nm, with peak emission at 808 nm, and it has near-infrared fluorescence properties. Notably, there was a significant difference in fluorescence values between benign and malignant cell lines (p < 0.0001). The malignant cell lines tested comprised CL1-5, A549, MDA-MB-468, U-87MG, MKN-7, and Hela, while benign cell lines were BEAS-2B, HUVEC, HSF, and VE. The most effective duration of action was identified as 30 min at a concentration of 5 µl. This optimal duration of action and concentration were consistent in patients with lung adenocarcinoma accompanied by pleural effusion and 5 µl. Of the 106 patients examined, 28 remained undiagnosed, 39 were diagnosed with malignant pleural effusions, and the remaining 39 with benign pleural effusions. Employing the new IR808@MnO staining method, the sensitivity stood at 74.4%, specificity at 79.5%, a positive predictive value of 69.2%, and a negative predictive value of 82.1%. The area under the ROC curve was recorded as 0.762 (95% CI: 0.652-0.872). The confusion matrix revealed a positive predictive value of 75.7%, a negative predictive value of 75.6%, a false positive rate of 22.5%, and a false negative rate of 26.3%. INTERPRETATION: The IR808@MnO fluorescent probe represents an efficient, sensitive, and user-friendly diagnostic tool for detecting malignant pleural fluid, underscoring its significant potential for clinical adoption.

Biomimetic NO Scavenging Hyaluronic Acid Nanoparticles Enable Targeted Delivery of MTX and Integrated Management of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a complicated chronic disorder of the immune system, featured with severe inflammatory joints, synovium hyperplasia, articular cartilage, and bone damage. In the RA microenvironment, RA-involved cells, overproduced nitric oxide (NO), and pro-inflammatory cytokines are highly interplayed and mutually reinforced, which form a vicious circle and play crucial roles in the formation and progression of RA. To comprehensively break the vicious circle and obtain the maximum benefits, we have developed neutrophil membrane-camouflaged NO scavenging nanoparticles based on an NO-responsive hyaluronic acid derivative for delivery of MTX. These multifunctional nanoparticles (NNO-NPs/MTX), by inheriting the membrane functions of the source cells, possess prolonged circulation and specific localization at the inflamed sites when administrated in the body. Remarkably, NNO-NPs/MTX can neutralize the pro-inflammatory cytokines via the outer membrane receptors, scavenge NO, and be responsively disassociated to release MTX for RA-involved cell regulation and HA for lubrication in the RA sites. In a collagen-induced arthritis mouse model, NNO-NPs/MTX exhibits a significant anti-inflammation effect and effectively alleviates the characteristic RA symptoms such as synovial hyperplasia and cartilage destruction, realizing the synergistic and boosted therapeutic outcome against intractable RA. Thus, NNO-NPs/MTX provides a promising and potent platform to integrately treat RA.

Garnet Structure-Activated Warm White Light Phosphors Ca3Al2Ge3O12: Dy3+, Eu3+ with Ultrahigh Thermal Stability and Tunable Luminescence.

A series of Ca3Al2Ge3O12: xDy3+, yEu3+ phosphors were successfully prepared by the high-temperature solid-phase method. The phase and morphology of the phosphors were studied by means of Rietveld refinement and scanning electron microscopy. The results show that the phase is pure, and the crystal structure is the Ia3̅d space group. In the Ca3Al2Ge3O12: xDy3+ phosphors, using 380 nm excitation, phosphors showed blue (4F9/2 → 6H15/2) and yellow (4F9/2 → 6H13/2) emission peaks at 481 and 581 nm, respectively. In Ca3Al2Ge3O12: xDy3+, yEu3+ phosphors, the energy transfer was inferred by the spectrum overlap of Dy3+ and Eu3+, and the lifetime attenuation was analyzed from the perspective of dynamics; finally, the band gap structure of the phosphors was analyzed by combining diffuse reflection spectra with the first principle, and the energy transfer mechanism and luminescence mechanism were elaborated by combining theory and practice. The transition from blue white light to red light can be achieved by tuning the range of y in Ca3Al2Ge3O12: 0.015Dy3+, yEu3+. Wherein, when y = 0.07, phosphors, the chromaticity coordinate of warm white CIE is (0.3932, 0.3203), the color temperature is 3093 K, and the warm white light is synthesized. The thermal stability of the synthesized warm white phosphors is 90.1% (423 K), the thermal sensing factors are Samax = 5.51 × 10-4 K-1 (303 K) and Srmax = 0.0359% K-1 (303 K), and the actual quantum efficiency is IQE = 52.48%. These results prove that Ca3Al2Ge3O12: Dy3+, Eu3+ have good application prospects as single-component warm w-LED devices.

A novel single-phase color tunable LiYGeO4:Dy3+, Eu3+ phosphor exhibiting warm white light and excellent thermal stability.

LiYGeO4 phosphors doped with Dy3+ and Eu3+ ions were synthesized using the solid phase method, and their color characteristics were adjustable. The bandgap value of LiYGeO4 calculated by diffuse reflection data is very close to the theoretical value of 3.669 eV, indicating that LiYGeO4 is an ideal candidate for doped rare earth activated ions. The analysis of the emission spectra and fluorescence attenuation curves of Dy3+ and Eu3+ co-doped LiYGeO4 phosphors revealed a clear energy transfer process: energy transfer from Dy3+ to Eu3+. Analysis of emission spectra and fluorescence attenuation curves revealed a transfer of energy from Dy3+ to Eu3+. This transfer mechanism is attributed to the dipole-dipole interactions. In addition, by constantly adjusting the doping levels of Dy3+ and Eu3+, a warm white phosphor with a color temperature of 3881 K was obtained. Finally, the emission intensity of the LiYGeO4:0.015Dy3+,0.02Eu3+ phosphor at 423 K was 86%, indicating that the phosphor has excellent thermal stability and 40% internal quantum efficiency, which proves the potential application of the LiYGeO4 phosphor in white light-emitting diodes (w-LEDs).

Effects of freeze-thaw cycles on soil greenhouse gas emissions: A systematic review.

In the context of global warming, increasingly widespread and frequent freezing and thawing cycles (FTCs) will have profound effects on the biogeochemical cycling of soil carbon and nitrogen. FTCs can increase soil greenhouse gas (GHG) emissions by reducing the stability of soil aggregates, promoting the release of dissolved organic carbon, decreasing the number of microorganisms, inducing cell rupture, and releasing carbon and nitrogen nutrients for use by surviving microorganisms. However, the similarity and disparity of the mechanisms potentially contributing to changes in GHGs have not been systematically evaluated. The present study consolidates the most recent findings on the dynamics of soil carbon and nitrogen, as well as GHGs, in relation to FTCs. Additionally, it analyzes the impact of FTCs on soil GHGs in a systematic manner. In this study, particular emphasis is given to the following: (i) the reaction mechanism involved; (ii) variations in soil composition in different types of land (e.g., forest, peatland, farmland, and grassland); (iii) changes in soil structure in response to cycles of freezing temperatures; (iv) alterations in microbial biomass and community structure that may provide further insight into the fluctuations in GHGs after FTCs. The challenges identified included the extension of laboratory-scale research to ecosystem scales, the performance of in-depth investigation of the coupled effects of carbon, nitrogen, and water in the freeze-thaw process, and analysis of the effects of FTCs through the use of integrated research tools. The results of this study can provide a valuable point of reference for future experimental designs and scientific investigations and can also assist in the analysis of the attributes of GHG emissions from soil and the ecological consequences of the factors that influence these emissions in the context of global permafrost warming.

Highly sensitive detection of multiple antiviral drugs using graphitized hydroxylated multi-walled carbon nanotubes/ionic liquids-based electrochemical sensors.

Global outbreaks and the spread of viral diseases in the recent years have led to a rapid increase in the usage of antiviral drugs (ATVs), the residues and metabolites of which are discharged into the natural environment, posing a serious threat to human health. There is an urgent need to develop sensitive and rapid detection tools for multiple ATVs. In this study, we developed a highly sensitive electrochemical sensor comprising a glassy carbon electrode (GCE) modified with graphitized hydroxylated multi-walled carbon nanotubes (G-MWCNT-OH) and 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6, IL) for the detection of six ATVs including famciclovir (FCV), remdesivir (REM), favipiravir (FAV), hydroxychloroquine sulfate (HCQ), cepharanthine (CEP) and molnupiravir (MOL). The morphology and structure of the G-MWCNT-OH/IL nanocomposites were characterized comprehensively, and the electroactive surface area and electron conductivity of G-MWCNT-OH/IL/GCE were determined using cyclic voltammetry and electrochemical impedance spectroscopy. The thermodynamic stability and non-covalent interactions between the G-MWCNT-OH and IL were evaluated through quantum chemical simulation calculations, and the mechanism of ATV detection using the G-MWCNT-OH/IL/GCE was thoroughly examined. The detection conditions were optimized to improve the sensitivity and stability of electrochemical sensors. Under the optimal experimental conditions, the G-MWCNT-OH/IL/GCE exhibited excellent electrocatalytic performance and detected the ATVs over a wide concentration range (0.01-120 µM). The limit of detections (LODs) were 42.3 nM, 55.4 nM, 21.9 nM, 15.6 nM, 10.6 nM, and 3.2 nM for FCV, REM, FAV, HCQ, CEP, and MOL, respectively. G-MWCNT-OH/IL/GCE was also highly stable and selective to the ATVs in the presence of multiple interfering analytes. This sensor exhibited great potential for enabling the quantitative detection of multiple ATVs in actual water environment.

Association of cardiometabolic and triglyceride-glucose index with left ventricular diastolic function in asymptomatic individuals.

BACKGROUND AND AIMS: Obesity and insulin resistance are associated with left ventricular diastolic dysfunction (LVDD) and increased risk of heart failure. Cardiometabolic index (CMI) and triglyceride glucose (TyG) are new indexes to assess visceral obesity and insulin resistance, respectively. The study aimed to investigate the clinical usefulness of these indexes for identifying LVDD individuals. METHODS AND RESULTS: Overall, 1898 asymptomatic individuals were included in this cross-sectional study. Participants underwent anthropometrics, serum biochemical evaluation, and echocardiography. Multiple linear regression analysis revealed that both indexes were independent determinants of diastolic parameters among females; while for males, CMI and TyG were not associated with A velocity. In the multivariate logistic analysis, the proportion of LVDD in the third and fourth quartiles of CMI remained significantly greater than that in the lowest quartile in females (Q3 vs. Q1: odds ratio (OR) = 2.032, 95% confidence interval (CI): 1.181-3.496; Q4 vs. Q1: OR = 2.393, 95% CI: 1.347-4.249); while in males, the incidence of LVDD was significantly greater only in the fourth quartile. For TyG, the presence of LVDD in the fourth quartile was significantly greater in both genders. The discriminant values between the CMI (AUC: 0.704, 95% CI: 0.668-0.739) and TyG (AUC: 0.717, 95% CI: 0.682-0.752) were similar in females. Both indexes performed better in females than in males to identify LVDD. CONCLUSION: The CMI and TyG might both serve as effective tools to identify LVDD in routine health check-ups in primary care, mainly in females. With simpler parameters, the CMI could be utilized in medically resource-limited areas.

Body conformation traits in early-lactation associated with clinical mastitis and lameness in lactating Chinese holstein cows.

BACKGROUND: Comprehending the correlation between body conformation traits of cows at the early stages of lactation and prevalent lactation diseases might facilitate the execution of selection and feeding strategies that prioritize cow health. This study aimed to evaluate the impact of body conformation traits on the incidence of clinical mastitis and lameness in Chinese Holstein cows. From a pasture herd of 1472 early lactating Chinese Holstein cows, we evaluated 20 body conformation traits. During lactation, this pasture herd was visited weekly to gather clinical mastitis and lameness data. A nine-point scale was used to determine the conformation traits of cows to clarify their linear characters, including frame capacity, rump (RU), feet and leg (FL), mammary system (MS), and dairy character. A longitudinal binary disease (0 = healthy; 1 = diseased) data structure was created by allocating disease records to adjacent official test dates. The impact of body conformation traits on the risk of developing diseases (clinical mastitis and lameness) was analyzed using the logistic regression models. RESULTS: Compared to cows with low total scores (75-79 points), those with high total scores (80-85 points) of body conformation traits had a significantly lower risk of mastitis (P < 0.001). The disease status (0 or 1: binary variable) of clinical mastitis in lactating cows was significantly impacted negatively by age (P < 0.05). The fore udder attachment (FUA), angularity, rear attachment height (RAH), and rear teat placement (RTP) were all significantly associated with clinical mastitis during lactation (P < 0.05). The rear leg-rear view (RLRV) was significantly correlated with correlated considerably (P < 0.05) with lameness during lactation. An ideal score of four points on the lameness risk dimension of the RLRV may indicate a low risk of lameness. Since the risk of mastitis decreased as this trait score increased, the RTP may be an ideal marker for mastitis risk. CONCLUSIONS: According to the study, clinical mastitis and lameness risks in cows can be estimated using their body conformation traits. Cows with more centrally located rear teats have a lower risk of mastitis. These results may help dairy farmers identify cows at high risk of disease early in lactation and aid in breeding for disease resistance in cows.

Gallic acid promotes macrophage phagosome acidification and phagolysosome formation by activating NLRP3/mTOR signaling pathway.

INTRODUCTION: Gallic acid (GA) has a good therapeutic effect in bacteriological inhibition and plays a variety of functions in maintaining the stability of the immune system. The aim of the present study was to investigate the effect of GA on the bactericidal activity of macrophages against Vibrio vulnificus (Vv). METHODS: A cell counting kit-8 (CCK-8) assay was carried out to test the cytotoxicity of GA on J774A.1 cells. Concentration of proinflammatory cytokines in J774A.1 cells were evaluated by ELISA. The internalization and degradation of Vv in the phagosomes were observed by transmission electron microscopy (TEM). The phagosome acidification and phagolysosome formation were detected to evaluate the bacteria-clearing function of J774A.1 cells. The bactericidal activity of GA in vivo was also investigated by collecting the survival time of Vv infected mice and observing the inflammatory infiltration of organs. RESULTS: Our results demonstrated that GA at 50 µM significantly inhibited the proinflammatory cytokines levels, promoted phagosome acidification and phagolysosome formation in J774A.1 cells with Vv infection. This may be related to the activation of NLRP3/mTOR signaling pathway. Additionally, GA treatment improves the survival and bactericidal activity of mice infected with Vv. CONCLUSIONS: In summary, GA exerts bactericidal activity against Vv infection by regulating the formation and acidification of phagocytic lysosomes in macrophages.

Comprehensive identification of pathogenic microbes and antimicrobial resistance genes in food products using nanopore sequencing-based metagenomics.

Foodborne pathogens, particularly antimicrobial-resistant (AMR) bacteria, remain a significant threat to global health. Given the limitations of conventional culture-based approaches, which are limited in scope and time-consuming, metagenomic sequencing of food products emerges as a promising solution. This method provides a fast and comprehensive way to detect the presence of pathogenic microbes and antimicrobial resistance genes (ARGs). Notably, nanopore long-read sequencing provides more accurate bacterial taxonomic classification in comparison to short-read sequencing. Here, we revealed the impact of food types and attributes (origin, retail place, and food processing methods) on microbial communities and the AMR profile using nanopore metagenomic sequencing. We analyzed a total of 260 food products, including raw meat, sashimi, and ready-to-eat (RTE) vegetables. Clostridium botulinum, Acinetobacter baumannii, and Vibrio parahaemolyticus were identified as the top three foodborne pathogens in raw meat and sashimi. Importantly, even with low pathogen abundance, higher percentages of samples containing carbapenem and cephalosporin resistance genes were identified in chicken and RTE vegetables, respectively. In parallel, our results demonstrated that fresh, peeled, and minced foods exhibited higher levels of pathogenic bacteria. In conclusion, this comprehensive study offers invaluable data that can contribute to food safety assessments and serve as a basis for quality indicators.

Risk Factors and Predictive Efficacy of Visceral Pleural Invasion in Lung Adenocarcinoma Patients with mGGN type.

Objective: To explore the risk factors and predictive effects of visceral pleural invasion in lung adenocarcinoma patients with mGGN type, in order to identify high-risk groups of visceral pleural invasion early, and to provide more references for targeted intervention and individualized treatment adjustment of high-risk groups based on the analysis of risk factors. Methods: The clinical data of 135 patients with mGGN-type lung adenocarcinoma who received surgical treatment in our hospital from January 2018 to December 2022 were selected from our hospital's medical record database for retrospective analysis. The patient information was entered by a two-person summary and analyzed after verification.The patients were divided into invasion group (60 cases) and non-invasion group (75 cases) according to the invasion of pleural viscera, which was helpful to analyze the difference of clinical features between the two groups. The independent risk factors for visceral pleural invasion in patients with mGGN lung adenocarcinoma were evaluated using univariate and multivariate factor methods, and receiver operating characteristic (ROC) curves were drawn to evaluate the clinical efficacy of these risk factors above alone and in combination in predicting of visceral pleural invasion risk. The larger the area under ROC curve, the higher the corresponding sensitivity and specificity, and the greater the predictive value for the risk of visceral pleural invasion in mGGN lung adenocarcinoma patients. Results: Univariate analysis showed that gender, family history of hypertension, location of focus, maximum diameter of solid component, proportion of solid component, pleural indentation, burr sign, bronchial and nodular route may be related to visceral pleural invasion in lung adenocarcinoma patients with mGGN type (P < .05). Multivariate Logistic regression analysis showed that pleural indentation (OR=2.49, 95%CI:1.17~4.58, P < .001) and abnormal broncho-nodular travel (OR=3.06, 95%CI: 1.35~7.02, P = .01) were the independent risk factors for visceral pleural invasion in lung adenocarcinoma patients with mGGN type (P < .05). ROC curve analysis results showed that pleural indentation (AUC=0.70, 95%CI: 0.65~0.79, P = .02), abnormal bronchial and nodular running relationship (AUC=0.74, 95%CI: 0.69~0.81, P = .01) could both be used to predict the visceral pleural invasion risk in lung adenocarcinoma patients with mGGN type, and combined prediction efficacy of both indexes (AUC=0.90, 95%CI: 0.85~0.97, P < .001) was better than single index. Conclusion: The occurrence of visceral pleural infiltration in patients with mGGN lung adenocarcinoma is related to the relationship between pleural indentation and bronchus and nodules. Combined with the above indicators, the risk of visceral pleural infiltration in patients can be effectively predicted, and early intervention and treatment can be performed on high-risk patients accordingly to effectively prevent and treat visceral pleural infiltration.