IGF2BP3 promotes glutamine metabolism of endometriosis by interacting with UCA1 to enhances the mRNA stability of GLS1.

BACKGROUND: Insulin like growth factor II mRNA binding protein 3 (IGF2BP3) has been implicated in numerous inflammatory and cancerous conditions. However, its precise molecular mechanisms in endometriosis (EMs) remains unclear. The aim of this study is to examine the influence of IGF2BP3 on the occurrence and progression of EMs and to elucidate its underlying molecular mechanism. METHODS: Efects of IGF2BP3 on endometriosis were confrmed in vitro and in vivo. Based on bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down assays and Fluorescent in situ hybridization (FISH) were used to show the association between IGF2BP3 and UCA1. Single-cell spatial transcriptomics analysis shows the expression distribution of glutaminase 1 (GLS1) mRNA in EMs. Study the effect on glutamine metabolism after ectopic endometriotic stromal cells (eESCs) were transfected with Sh-IGF2BP3 and Sh-UCA1 lentivirus. RESULTS: Immunohistochemical staining have revealed that IGF2BP3 was upregulated in ectopic endometriotic lesions (EC) compared to normal endometrial tissues (EN). The proliferation and migration ability of eESCs were greatly reduced by downregulating IGF2BP3. Additionally, IGF2BP3 has been observed to interact with urothelial carcinoma associated 1 (UCA1), leading to increased stability of GLS1 mRNA and subsequently enhancing glutamine metabolism. Results also demonstrated that IGF2BP3 directly interacts with the 3' UTR region of GLS1 mRNA, influencing its expression and stability. Furthermore, UCA1 was able to bind with c-MYC protein, stabilizing c-MYC mRNA and consequently enhancing GLS1 expression through transcriptional promotion. CONCLUSION: These discoveries underscored the critical involvement of IGF2BP3 in the elevation and stability of GLS1 mRNA in the context of glutamine metabolism by interacting with UCA1 in EMs. The implications of our study extended to the identification of possible therapeutic targets for individuals with EMs.

One-Shot Dual-Detection-Based Single-Molecule Super-Resolution Imaging Method for Real-Time Observation of Spatiotemporal Catalytic Activity Variations on the Plasmonic Gold Nanoparticle Surface.

Understanding the relationship between the surface properties of a single plasmonic nanoparticle and its catalytic performance is critical for developing highly efficient nanocatalysts. In this study, a one-shot dual-detection-based single-molecule super-resolution imaging method in the evanescent field was developed to observe real-time spatiotemporal catalytic activity on a single plasmonic gold nanoparticle (AuNP) surface. The scattering intensity of AuNPs and the fluorescence of resorufin molecules produced on the AuNP surface were obtained simultaneously to investigate the relationship between nanoparticles and catalytic reactions at a single-molecule level. Chemisorbed adsorbates (i.e., catalytic product and resorufin) changed the electron density of individual AuNPs throughout the catalytic cycle, resulting in the fluctuation of the scattering intensity of individual AuNPs, which was attributed to the electron transfer between reactant resazurin molecules and AuNPs. The increase in the electron density of individual AuNPs affected the catalytic reaction rate. Furthermore, sequential mapping of individual catalytic events at the subdiffraction limit resolution was completed for real-time surface dynamics and spatiotemporal activity variations on the single AuNP surface. The developed method can aid in understanding surface-property-dependent catalytic kinetics and facilitate the development of nanoparticle-based heterogeneous catalysts at subdiffraction limit resolution.

Long-term PM2.5 exposure associated with severity of angina pectoris and related health status in patients admitted with acute coronary syndrome: Modification effect of genetic susceptibility and disease history.

Long-term particulate matter with aerodynamic diameters ≤2.5 µm (PM2.5) exposure has been associated with the occurrence of acute coronary syndrome (ACS). However, the impact of PM2.5 exposure and its components on the severity of angina pectoris and disease-related health status in patients hospitalized for ACS is understudied. To assess the association between long-term exposure to PM2.5 components and the angina pectoris severity in ACS patients, as well as the modification effects of genetic factors and disease history in north China. During 2017-2019, 6729 ACS patients were collected in Shandong Province and Beijing, with their angina pectoris severity evaluated using Seattle Angina Questionnaire (SAQ). The 0-3 years' average concentrations of PM2.5 and its five major components were assigned to each patient's residential address. Linear mixed-effects model, weighted quantile regression, and quantile g-computation were used to estimate the effects of both single and joint associations between PM2.5 components and SAQ scores. The interactive effect was estimated by polygenic risk scores and disease history. For each interquartile range increase in PM2.5, the overall SAQ score changed by -3.71% (95%CI: -4.54% to -2.88%), with score of angina stability more affected than angina frequency and other dimensions of angina pectoris severity. Sulfate and ammonium were major contributors to the effect of PM2.5 exposure. Significant modification effect was only observed for disease history, especially for the dimension of physical limitation. Among a series of pre-existing diseases, patients with a family history of coronary artery disease, previous percutaneous coronary intervention or coronary artery bypass grafting, and stroke were more susceptible to PM2.5 exposure than others. Greater exposure to PM2.5 is associated with more serious angina pectoris and worse disease-related health status in ACS patients. Public health and clinical priority should be given to cutting down key effective components and protecting highly vulnerable individuals.

Activity of thonningianin A against Candida albicans in vitro and in vivo.

Fungal infections are increasing rapidly, and antifungal agents used in clinics are limited. Therefore, novel antifungal agents with high efficiency are urgently required. In this study, we investigated the antifungal activity of thonningianin A (THA), a natural compound that is widely found in plants. We first determined the activity of THA against Candida albicans, one of the most common fungal pathogens, and found that THA showed antifungal activity against all C. albicans tested, including several fluconazole-resistant isolates. THA also inhibits the growth of non-Candida albicans species. In addition, THA displayed antibiofilm activity and could not only inhibit biofilm formation but also destroy mature biofilms. The in vivo antifungal efficacy of THA was confirmed in a Galleria mellonella infection model. Further studies revealed that THA could enhance intracellular reactive oxygen species (ROS) production and regulate the transcription of several redox-related genes. Specifically, caspase activity and expression of CaMCA1, a caspase-encoding gene in C. albicans, were remarkably increased upon THA treatment. Consistent with this, in the presence of THA, the Camca1 null mutant displayed higher survival rates and reduced caspase activity compared to the wild-type or CaMCA1-reintroduced strains, indicating an important role of CaMCA1 in the antifungal activity of THA. Taken together, our results indicate that THA possesses excellent antifungal activity and may be a promising novel antifungal candidate. KEY POINTS: • THA exhibits activity against Candida species, including fluconazole-resistant isolates • THA inhibits biofilm formation and destroys mature biofilm • Elevated ROS production and CaMCA1-mediated caspase activity are involved in the antifungal mechanisms of THA.

Crucial Involvement of Heme Biosynthesis in Vegetative Growth, Development, Stress Response, and Fungicide Sensitivity of Fusarium graminearum.

Heme biosynthesis is a highly conserved pathway from bacteria to higher animals. Heme, which serves as a prosthetic group for various enzymes involved in multiple biochemical processes, is essential in almost all species, making heme homeostasis vital for life. However, studies on the biological functions of heme in filamentous fungi are scarce. In this study, we investigated the role of heme in Fusarium graminearum. A mutant lacking the rate-limiting enzymes in heme synthesis, coproporphyrinogen III oxidase (Cpo) or ferrochelatase (Fc), was constructed using a homologous recombination strategy. The results showed that the absence of these enzymes was lethal to F. graminearum, but the growth defect could be rescued by the addition of hemin, so we carried out further studies with the help of hemin. The results demonstrated that heme was required for the activity of FgCyp51, and its absence increased the sensitivity to tebuconazole and led to the upregulation of FgCYP51 in F. graminearum. Additionally, heme plays an indispensable role in the life cycle of F. graminearum, which is essential for vegetative growth, conidiation, external stress response (especially oxidative stress), lipid accumulation, fatty acid ß-oxidation, autophagy, and virulence.

Genome-Wide Identification and Expression Analysis of Kiwifruit Leucine-Rich Repeat Receptor-Like Proteins Reveal Their Roles in Biotic and Abiotic Stress Responses.

Leucine-rich repeat receptor-like proteins (LRR-RLPs), a major group of receptor-like proteins in plants, have diverse functions in plant physiology, including growth, development, signal transduction, and stress responses. Despite their importance, the specific roles of kiwifruit LRR-RLPs in response to biotic and abiotic stresses remain poorly understood. In this study, we performed family identification, characterization, transcriptome data analysis, and differential gene expression analysis of kiwifruit LRR-RLPs. We identified totals of 101, 164, and 105 LRR-RLPs in Actinidia chinensis 'Hongyang', Actinidia eriantha 'Huate', and Actinidia chinensis 'Red5', respectively. Synteny analysis revealed that the expansion of kiwifruit LRR-RLPs was primarily attributed to segmental duplication events. Based on RNA-seq data from pathogen-infected kiwifruits, we identified specific LRR-RLP genes potentially involved in different stages of pathogen infection. Additionally, we observed the potential involvement of kiwifruit LRR-RLPs in abiotic stress responses, with upstream transcription factors possibly regulating their expression. Furthermore, protein interaction network analysis unveiled the participation of kiwifruit LRR-RLP in the regulatory network of abiotic stress responses. These findings highlight the crucial roles of LRR-RLPs in mediating both biotic and abiotic stress responses in kiwifruit, offering valuable insights for the breeding of stress-resistant kiwifruit varieties.

Screening and Application of DNA Aptamers for Heparin-Binding Protein.

Rapid detection of heparin-binding protein (HBP) is essential for timely intervention in sepsis cases. Current detection techniques are usually antibody-based immunological methods, which have certain problems, such as complexity and slow detection, and fall short in meeting the urgency of clinical needs. The application of an aptamer can address these concerns well. In this study, HBP-specific DNA aptamers were screened first. Among which, Apt-01, Apt-02, and Apt-13 had a high affinity for HBP, exhibiting impressive KD values of 3.42, 1.44, and 1.04 nmol/L, respectively. Then, the aptamer of HBP and its partially complementary primer probe were combined to form double-stranded DNA (dsDNA) and synthesize a circular DNA template. The template is complementary to the primer probe, but due to the presence of dsDNA, ExoIII cleaves C2-13 as an RCA primer probe, rendering the template unable to recognize the primer probe and preventing the RCA reaction from proceeding. When the target is present, it competes with the adapter for recognition and releases C2-13, exposing its 3' end. After initiating the RCA at room temperature and reacting with SYBR GreenII at 37 °C for 20 min, fluorescence changes can be observed and quantitatively analyzed at a 530 nm wavelength, achieving quantitative biological analysis. Apt-01 was used to develop a fluorescent biosensor for HBP detection, which exhibited a good linear range (0.01 nmol/L to 10 nmol/L) and detection limit (0.0056 nmol/L). This advancement holds the potential to lay a solid groundwork for pioneering sensitive and specific methods for HBP detection and to significantly enhance the diagnostic processes for sepsis.

Ectopic endometriotic stromal cells-derived lactate induces M2 macrophage polarization via Mettl3/Trib1/ERK/STAT3 signalling pathway in endometriosis.

Endometriosis is a gynaecological condition characterized by the growth of endometrium-like tissues within and outside of the pelvic cavity. Recent studies have demonstrated that aberrant infiltration of M2 macrophages is mainly responsible for the establishment of endometriotic lesions. A growing body of evidence shows that glycolysis and lactate accumulation have great impact on the regulation of immunomicroenvironment. However, the communication signal between glycolysis and macrophages is poorly defined in endometriosis. Hereby, we investigate the correlation between glycolysis and M2 macrophage infiltration in endometriosis. Next, we confirm that lactate is pivotal factor that drives macrophage M2-polarization to promote endometriotic stromal cells invasion in vitro and in vivo. In addition, we also identify that the activation of Mettl3 and its target gene Trib1 promote M2 macrophage polarization. Moreover, we also demonstrate that Trib1 induce M2 macrophage polarization via the activation of ERK/STAT3 signalling pathway. Finally, by injecting 2-DG into endometriosis mice model, we show that the restrain of glycolysis significantly reduces the progression of endometriosis, which provides evidence for lactate as a potential therapeutic strategy for the prevention and treatment of endometriosis.

Clinical features and prognosis of acute-on-chronic liver failure in patients with recompensated cirrhosis.

BACKGROUND: There are few studies on acute-on-chronic liver failure (ACLF) in patients with recompensated cirrhosis. This study was aimed to investigate the clinical features of ACLF patients with recompensated cirrhosis. METHODS: A total of 461 ACLF patients were enrolled and divided into three groups: compensated, recompensated, and decompensated cirrhosis with ACLF. The baseline clinical data and 1-year survival rates were compared among the three groups. RESULTS: Compared with the decompensated group, in the recompensated group, the levels of hemoglobin, albumin, and serum sodium were significantly higher and the white blood cell count, international normalized ratio, and incidence of respiratory failure were significantly lower; there were no evident differences in other organ failures. The proportion of patients with ACLF grade 3 and 1-year survival rates significantly differed between the two groups. Conversely, compared with the compensated group, in the recompensated group, the platelet and total bilirubin levels were significantly lower and the proportion of patients with ACLF grade 1 was significantly higher. However, other clinical indicators or 1-year survival rates did not significantly differ between the two groups. CONCLUSIONS: Compared with patients who developed ACLF with decompensated cirrhosis, those who developed ACLF with recompensated cirrhosis had a less severe condition, lower incidence of respiratory failure, and better 1-year prognosis. However, the baseline clinical features and prognosis were similar between ACLF patients with recompensated and compensated cirrhosis. TRIAL REGISTRATION: Chinese clinical trials registry: ChiCTR1900021539.

In vitro antifungal activity of Shikonin against Candida albicans by inducing cellular apoptosis and necrosis.

BACKGROUND: Our previous studies showed that Shikonin (SK) had a strong anti-Candida albican (C. albicans) activity, especially against some fluconazole-resistant strains, which is probably due to the oxidative damage of SK to C. albicans. METHODS AND RESULTS: In this study, we expanded the antifungal spectrum and evaluate the toxicity of SK. The results indicated that SK also exhibited potent invitro antifungal activities against other pathogenic fungi such as other Candida, Aspergillus, Cryptococcus, and Dermatophytes, but did not display apparent toxicity to the mammalian cells, suggesting that SK is safe to be a potential antifungal drug. Furtherly, we analyze the exact mechanism of SK against C. albicans. We found that SK could induce a series of apoptosis characteristics, including phosphatidylserine externalization, chromatin condensation and fragmentation, decreased cytochrome c oxidase activity as well as caspase activation. CONCLUSIONS: In summary, this study highlighted the antifungal activity and mechanism of SK against C. albicans, providing a potential therapeutic strategy for C. albicans infection.

Real-time six-dimensional spatiotemporal tracking of single anisotropic nanoparticles in live cells by integrated multifunctional light-sheet nanoscopy.

An integrated multifunctional light-sheet nanoscopy (iMLSN) combined with differential interference contrast, total internal reflection, epifluorescence, a super-resolution radial fluctuation-stream module, and a wavelength-dependent light sheet was developed to simultaneously realize the six-dimensional (6D) vector-valued (three coordinates + rotational dynamics (azimuth and elevation angles) + transport speed) tracking of anisotropic nanoparticles in single living cells. The wavelength-dependent asymmetric scattering of light by gold nanorods was used to trigger signals depending on the polarizer angle, and real-time photo-switching was achieved by turning the polarizer, obtaining a series of super-resolution images, and tracking using different polarization directions and two channels. This technique was employed to directly observe native gold nanorods (AuNRs; 5 nm diameter × 15 nm length) and surface-functionalized AuNRs during their endocytosis and transport at the upper and attaching side membrane regions of single living cells, revealing that the AuNRs bound to the membrane receptors. The nanorods were subsequently internalized and transported away from the original entry spots. Detailed dynamic information regarding the rotation properties and endocytosis speed during the transmembrane process was also acquired for each region. The developed technique can be considered useful for the real-time monitoring of intracellular transport at various regions in single living cells, as well as for 6D vector-valued non-fluorescence super-resolution imaging and tracking.

Synergistic modification of collagen structure using ionic liquid and ultrasound to promote the production of DPP-IV inhibitory peptides.

BACKGROUND: Dual modification of collagen was performed using ionic liquid (IL) and ultrasound (US) to modulate the activity of collagen hydrolyzed peptides and reveal the production mechanism of cowhide-derived dipeptidyl peptidase (DPP-IV) inhibitory peptides. RESULTS: The results revealed that dual modification (IL + US) significantly improved the hydrolytic degree of collagen (P < 0.05). Meanwhile, IL and US tended to promote the break of hydrogen bonds, but inhibit the crosslinking between collagens. The double modification reduced the thermal stability and accelerated the exposure of tyrosine and phenylalanine of collagen, and improved the proportion of small molecular (< 1 kDa) peptides in collagen hydrolysates. Interestingly, the hydrophobic amino acid residues and DPP-IV inhibitory activity of collagen peptides with small molecular weight (< 1 kDa) was increased further under the combination of IL and US. CONCLUSION: Enhanced hypoglycemic activity of collagen peptides can be attained through the dual modification of IL and US. © 2023 Society of Chemical Industry.

Enterotoxigenic Bacteroidesfragilis Promotes Intestinal Inflammation and Malignancy by Inhibiting Exosome-Packaged miR-149-3p.

BACKGROUND & AIMS: Enterotoxigenic Bacteroides fragilis (ETBF) is strongly associated with the occurrence of inflammatory bowel disease (IBD), colitis-associated colorectal cancer, and colorectal cancer (CRC). However, the mechanism of ETBF-induced intestinal inflammation and tumorigenesis remains unclear. METHODS: microRNA sequencing was used to detect the differentially expressed microRNAs in both ETBF-treated cells and exosomes derived from ETBF-inoculated cells. Cell Counting Kit 8 assays were used to evaluate the effect of ETBF and exosomes on CRC cell proliferation. The biological role and mechanism of ETBF-mediated miR-149-3p in colitis and colon carcinogenesis were determined both in vitro and in vivo. RESULTS: ETBF promoted CRC cell proliferation by down-regulating miR-149-3p both in vitro and in vivo. ETBF-down-regulated miR-149-3p depended on METTL14-mediated N6-methyladenosine methylation. As the target gene of miR-149-3p, PHF5A transactivated SOD2 through regulating KAT2A messenger RNA alternative splicing after ETBF treatment in CRC cells. miR-149-3p could be released in exosomes and mediated intercellular communication by modulating T-helper type 17 cell differentiation. The level of plasma exosomal miR-149-3p was gradually decreased from healthy control individuals to patients with IBD and CRC. miR-149-3p, existing in plasma exosomes, negatively correlated with the abundance of ETBF in patients with IBD and CRC. CONCLUSIONS: Exosomal miR-149-3p derived from ETBF-treated cells facilitated T-helper type 17 cell differentiation. ETBF-induced colorectal carcinogenesis depended on down-regulating miR-149-3p and further promoting PHF5A-mediated RNA alternative splicing of KAT2A in CRC cells. Targeting the ETBF/miR-149-3p pathway presents a promising approach to treat patients with intestinal inflammation and CRC with a high amount of ETBF.

Minimizing the Optical Illusion of Nanoparticles in Single Cells Using Four-Dimensional Cuboid Multiangle Illumination-Based Light-Sheet Super-Resolution Imaging.

Although light-sheet-based super-resolution microscopy is an excellent detection technique for biological samples because of minimal photodamage, uneven light paths due to solid-angle illumination limits it, resulting in an optical illusion. Furthermore, the optical illusion limits the observations of individual molecules in diffraction. In this study, a four-dimensional cuboid multiangle illumination-based light-sheet super-resolution (4D CMLS) imaging system was developed to minimize optical illusions in cells. The lab-built 4D CMLS imaging system was integrated with total internal reflection fluorescence and a differential interference contrast microscope. A specially designed rotatable cuboid prism simply overcame the optical illusion by rotating a specimen on the prism to change the direction of light coming from an illumination lens. 4D CMLS reconstructed images of nanoparticles of different sizes were acquired in multi-illumination angles of 0°, 90°, 180°, and 270°. Additionally, a 4D multiangle illumination-based algorithm was created to select the optimal illumination angle by combining three-dimensional super-resolution imaging with multiangle observation, even in the presence of obstacles. The 4D CMLS imaging method demonstrates the in-depth 4D observation of samples at an optimum angle that can be used in various applications, such as single-molecule and subcellular organelle observations in single cells at subdiffraction limit resolutions that describe the scenario of nature.

Leaf angle: a target of genetic improvement in cereal crops tailored for high-density planting.

High-density planting is an effective measure for increasing crop yield per unit land area. Leaf angle (LA) is a key trait of plant architecture and a target for genetic improvement of crops. Upright leaves allow better light capture in canopy under high-density planting, thus enhancing photosynthesis efficiency, ventilation and stress resistance, and ultimately higher grain yield. Here, we summarized the latest progress on the cellular and molecular mechanisms regulating LA formation in rice and maize. We suggest several standing out questions for future studies and then propose some promising strategies to manipulate LA for breeding of cereal crops tailored for high-density planting.

Comparative analysis of absorbed ingredients and metabolites, and pharmacokinetic studies of Zhimu-Huangbai herb pair in the plasma of normal and type 2 diabetes mellitus rats by UHPLC-linear trap quadrupole-orbitrap MS and LC-MS/MS.

A new rapid ultra-high-performance liquid chromatography coupled with linear trap quadrupole orbitrap mass spectrometry method was established for the qualitative analysis of absorbed ingredients and metabolites of Zhimu-Huangbai herb pair, which is used to treat type 2 diabetes mellitus. A total of 16 absorbed ingredients and 11 metabolites were identified in normal and type 2 diabetes mellitus rats, respectively. Such findings indicated that the diabetic model had no effect on the type of components in plasma. Seven absorbed ingredients and 11 metabolites were first identified after the oral administration of Zhimu-Huangbai herb pair. Thereafter, ultra-high-performance liquid chromatography coupled with linear trap quadrupole orbitrap mass spectrometry and liquid chromatography-API4000+ triple quadrupole mass spectrometer methods were established and validated for pharmacokinetic comparative studies of seven major bioactive components in normal and type 2 diabetes mellitus rats. Partial pharmacokinetic parameters in the plasma of type 2 diabetes mellitus rats were significantly different from those in normal rats. To our knowledge, this is the first comparison of absorbed ingredients and metabolites of Zhimu-Huangbai herb pair, and its use in pharmacokinetic studies between normal and type 2 diabetes mellitus rats. Ultimately, our findings provide insights into the clinical usage of Zhimu-Huangbai herb pair.

ZmSPL10/14/26 are required for epidermal hair cell fate specification on maize leaf.

The epidermal hair and stomata are two types of specialized structures on the surface of plant leaves. On mature maize leaves, stomatal complexes and three types of hairs are distributed in a stereotyped pattern on the adaxial epidermis. However, the spatiotemporal relationship between epidermal hair and stomata development and the regulatory mechanisms governing their formation in maize remain largely unknown. Here, we report that three homologous ZmSPL transcription factors, ZmSPL10, ZmSPL14 and ZmSPL26, act in concert to promote epidermal hair fate on maize leaf. Cytological analyses revealed that Zmspl10/14/26 triple mutants are completely glabrous, but possess ectopic stomatal files. Strikingly, the precursor cells for prickle and bicellular hairs are transdifferentiated into ectopic stomatal complexes in the Zmspl10/14/26 mutants. Molecular analyses demonstrated that ZmSPL10/14/26 bind directly to the promoter of a WUSCHEL-related homeobox gene, ZmWOX3A, and upregulate its expression in the hair precursor cells. Moreover, several auxin-related genes are downregulated in the Zmspl10/14/26 triple mutants. Our results suggest that ZmSPL10/14/26 play a key role in promoting epidermal hair fate on maize leaves, possibly through regulating ZmWOX3A and auxin-related gene expression, and that the fates of epidermal hairs and stomata are switchable.

Identification of ZmNF-YC2 and its regulatory network for maize flowering time.

Flowering time is an important agronomic trait that determines the distribution and adaptation of plants. The accurate prediction of flowering time in elite germplasm is critical for maize breeding. However, the molecular mechanisms underlying the photoperiod response remain elusive in maize. Here we cloned the flowering time-controlling gene, ZmNF-YC2, by map-based cloning and confirmed that ZmNF-YC2 is the nuclear transcription factor Y subunit C-2 protein and a positive regulator of flowering time in maize under long-day conditions. Our results show that ZmNF-YC2 promotes the expression of ZmNF-YA3. ZmNF-YA3 negatively regulates the transcription of ZmAP2. ZmAP2 suppresses the expression of ZMM4 to delay flowering time. We then developed a gene regulatory model of flowering time in maize using ZmNF-YC2, ZmNF-YA3, ZmAP2, ZMM4, and other key genes. The cascading regulation by ZmNF-YC2 of maize flowering time has not been reported in other species.

Hepatitis B-related acute-on-chronic liver failure induced by hepatotropic viral insult is associated with worse prognosis than that induced by non-virus insult.

BACKGROUND: The manifestations and prognoses of acute-on-chronic liver failure (ACLF) with different precipitating events remain heterogeneous. We aimed to investigate the characteristics and prognosis of patients with hepatotropic viral insult (HVI)-induced hepatitis B-related ACLF (HBV-ACLF). METHODS: 452 patients with confirmed diagnosis of ACLF were screened in three medical centers in China, and 203 HBV-ACLF patients with definite acute precipitating events were retrospectively analyzed. According to the precipitating events, HBV-ACLF patients induced by HBV reactivation and super-infection with HAV were classified as the hepatotropic viral insult group and those induced by other factors, as the non-virus insult (NVI) group. The clinical characteristics, predictive scoring model, and prognosis of the two groups were compared. RESULTS: Hepatitis B virus reactivation accounted for the largest proportion (39.9%) among all precipitating events. Exacerbation time frame of the HVI group was significantly longer than that of the NVI group (20 days vs. 10 days, P < 0.001). Comparison of intergroup prognosis showed that there was no significant difference in the 28 day mortality (20.9 vs. 13.7%, P = 0.125), while the 90 day and 1 year mortality in the HVI group were higher than those in the NVI group (36.3 vs. 24.4%, P = 0.014; 39.5% vs. 27.5%, P = 0.020, respectively). In the HVI group, the lactic acid-free APASL-ACLF Research Consortium (AARC) had better predictive value for 90 day mortality (0.741). CONCLUSIONS: The 90 day and 1 year survival rate was lower in HBV-ACLF patients induced by HVI than by NVI. The lactate-free AARC score was a better predictor of short- and long-term prognosis in patients with HVI-induced HBV-ACLF.

Gestational systolic blood pressure trajectories and risk of adverse maternal and perinatal outcomes in Chinese women.

BACKGROUND: Associations between trajectories of systolic blood pressure (SBP) during pregnancy and pregnant outcomes remain unclear and disparate. METHODS: Data of 20,353 mothers without chronic hypertension and who delivered live singletons between January, 2014 and November, 2019, was extracted from Taicang register-based cohort. Based on SBP measured during 10 to 40 weeks of gestation, SBP trajectories were explored using latent class growth mixture model, and their associations with maternal and neonatal outcomes were assessed by logistic regression analyses. RESULTS: Six heterogeneous SBP trajectories were identified: low delayed-increasing (7.47%), low reverse-increasing (21.88%), low-stable (19.13%), medium-stable (21.64%), medium reverse-increasing (16.47%), and high stable (13.41%) trajectories. The high-stable trajectory had SBP around 125 mmHg in the 10th gestational week, and increased slightly onwards. When compared with the low-stable trajectory, the high-stable trajectory had maximally adjusted odds ratio (95% confidence interval) of 5.28 (2.76-10.10), 1.30 (1.13-1.50), 1.53 (1.12-2.08), 1.32 (1.06-1.65) and 1.64 (1.08-2.48) for gestational hypertension (GH), early-term delivery (ETD), preterm delivery (PTD), small for gestational age and low birth weight (LBW), respectively. Besides, the medium reverse-increasing trajectory showed significantly increased risk of GH and ETD, while the medium-stable trajectory had significantly elevated risk of ETD and PTD. Notably, SBP trajectories slightly but significantly improved risk discrimination of GH, ETD and LBW, over traditional risk factors. CONCLUSION: Women with different SBP trajectories were at varied risk of adverse maternal and fetal outcomes. Meanwhile, our study suggested that BP monitoring during pregnancy is necessary, especially for women with high SBP in early pregnancy or upward trajectory.