Integration of C3H15-mediated transcriptional and post-transcriptional regulation confers plant thermotolerance in Arabidopsis.

Heat stress is an environmental factor that significantly threatens crop production worldwide. Nevertheless, the molecular mechanisms governing plant responses to heat stress are not fully understood. Plant zinc finger CCCH proteins have roles in stress responses as well as growth and development through protein-RNA, protein-DNA, and protein-protein interactions. Here, we reveal an integrated multi-level regulation of plant thermotolerance that is mediated by the CCCH protein C3H15 in Arabidopsis. Heat stress rapidly suppressed C3H15 transcription, which attenuated C3H15-inhibited expression of its target gene HEAT SHOCK TRANSCRIPTION FACTOR A2 (HSFA2), a central regulator of heat stress response (HSR), thereby activating HEAT SHOCK COGNATE 70 (HSC70.3) expression. The RING-type E3 ligase MED25-BINDING RING-H2 PROTEIN 2 (MBR2) was identified as an interacting partner of C3H15. The mbr2 mutant was susceptible to heat stress compared to wild-type plants, whereas plants overexpressing MBR2 showed increased heat tolerance. MBR2-dependent ubiquitination mediated the degradation of phosphorylated C3H15 protein in the cytoplasm, which was enhanced by heat stress. Consistently, heat sensitivities of C3H15 overexpression lines increased in MBR2 loss-of-function and decreased in MBR2 overexpression backgrounds. Heat stress-induced accumulation of HSC70.3 promoted MBR2-mediated degradation of C3H15 protein, implying that an auto-regulatory loop involving C3H15, HSFA2, and HSC70.3 regulates HSR. Heat stress also led to the accumulation of C3H15 in stress granules (SGs), a kind of cytoplasmic RNA granule. This study advances our understanding of the mechanisms plants use to respond to heat stress, which will facilitate technologies to improve thermotolerance in crops.

A DE1 BINDING FACTOR 1-GLABRA2 module regulates rhamnogalacturonan I biosynthesis in Arabidopsis seed coat mucilage.

The mucilage surrounding hydrated Arabidopsis thaliana seeds is a specialized extracellular matrix composed mainly of the pectic polysaccharide rhamnogalacturonan I (RG-I). Although, several genes responsible for RG-I biosynthesis have been identified, the transcriptional regulatory mechanisms controlling RG-I production remain largely unknown. Here we report that the trihelix transcription factor DE1 BINDING FACTOR 1 (DF1) is a key regulator of mucilage RG-I biosynthesis. RG-I biosynthesis is significantly reduced in loss-of-function mutants of DF1. DF1 physically interacts with GLABRA2 (GL2) and both proteins transcriptionally regulate the expression of the RG-I biosynthesis genes MUCILAGE MODIFIED 4 (MUM4) and GALACTURONOSYLTRANSFERASE-LIKE5 (GATL5). Through chromatin immunoprecipitation-quantitative PCR and transcriptional activation assays, we uncover a cooperative mechanism of the DF1-GL2 module in activating MUM4 and GATL5 expression, in which DF1 binds to the promoters of MUM4 and GATL5 through interacting with GL2 and facilitates the transcriptional activity of GL2. The expression of DF1 and GL2 is directly regulated by TRANSPARENT TESTA GLABRA2 (TTG2) and, in turn, DF1 directly represses the expression of TTG2. Taken together, our data reveal that the transcriptional regulation of mucilage RG-I biosynthesis involves a regulatory module, comprising DF1, GL2, and TTG2.

Ubiquitinated DA1 negatively regulates vascular cambium activity through modulating the stability of WOX4 in Populus.

Activity of the vascular cambium gives rise to secondary xylem for wood formation in trees. The transcription factor WUSCHEL-related HOMEOBOX4 (WOX4) is a central regulator downstream of the hormone and peptide signaling pathways that maintain cambial activity. However, the genetic regulatory network underlying WOX4-mediated wood formation at the post-transcriptional level remains to be elucidated. In this study, we identified the ubiquitin receptor PagDA1 in hybrid poplar (Populus alba × Populus glandulosa clone 84K) as a negative regulator of wood formation, which restricts cambial activity during secondary growth. Overexpression of PagDA1 in poplar resulted in a relatively reduced xylem due to decreased cambial cell division. By contrast, mutation of PagDA1 by CRISPR/Cas9 resulted in an increased cambial cell activity and promoted xylem formation. Genetic analysis demonstrated that PagDA1 functions antagonistically in a common pathway as PagWOX4 to regulate cambial activity. We propose that PagDA1 physically associates with PagWOX4 and modulates the degradation of PagWOX4 by the 26S proteasome. Moreover, genetic analysis revealed that PagDA1 exerts its negative effect on cambial development by modulating the stability of PagWOX4 in a ubiquitin-dependent manner mediated by the E3 ubiquitin ligase PagDA2. In sum, we have identified a cambial regulatory protein complex, PagDA1-PagWOX4, as a potential target for wood biomass improvement.

Cognitive shadows in perimenopause: linking subjective cognitive decline (SCD) to menopausal symptom severity.

OBJECTIVE: As women approach perimenopause, the incidence of Subjective Cognitive Decline (SCD) rises. This study aims to investigate the association between SCD and the severity of perimenopausal symptoms. SETTING: Conducted at The Affiliated Hospital of Guizhou Medical University Menopause Clinic from November 2022 to June 2023. Participants, aged 40-55 years, were classified as perimenopausal using the STRAW + 10 criteria. METHODS: SCD was assessed separately using the Chinese version of the SCD-Q9 scale and the SCD International Working Group (SCD-I) conceptual framework, while perimenopausal symptoms were evaluated with the Modified Kupperman Index (MKI). Linear relationships between MKI scores and SCD-Q9 scores were clarified using both univariate and multivariate linear regression analyses. Additionally, a multivariate Logistic regression analysis was conducted to examine the association between MKI scores and SCD classification based on SCD-I criteria. MAIN OUTCOME MEASURES: The primary outcomes were the Modified Kupperman Index scores, SCD-Q9 questionnaire scores, and the diagnosis of SCD based on SCD-I criteria. RESULTS: Among 101 participants, the average MKI score was 18.90 ± 9.74, and the average SCD-Q9 score was 4.57 ± 2.29. Both univariate and multivariate linear regressions demonstrated a positive correlation between these scores. A multivariate Logistic regression analysis, using MKI as the independent variable and SCD-I criteria classification as the dependent variable, revealed a significant positive association. CONCLUSIONS: A notable association exists between SCD and perimenopausal symptoms severity. This underscores the potential clinical importance of addressing perimenopausal symptoms to mitigate SCD risks in women. Further studies should focus on clarifying the causality between these factors.

Waiting for self-healing as a primary management strategy for lower lip mucoceles.

OBJECTIVES: Oral mucoceles are most frequently encountered on the lower lip. A variety of treatment options are currently employed, including surgical excision, pharmacological injections, and laser therapy. However, each of these approaches may introduce risks and potential complications. Clinical practice has demonstrated a potential for self-healing in lower lip mucoceles, making a conservative observational approach more appealing. This research is a prospective study aimed at evaluating the self-healing capacity of lower lip mucoceles. METHODS: In this prospective study, patients with mucoceles were encouraged to intentionally delay medical intervention and to wait for self-healing. Disappearance of the mucocele for at least 3 months was defined as self-healing. RESULTS: Thirty patients with lower lip mucoceles were included. With no intervention, 24 patients (80%) reported self-healing of lower lip mucoceles. The mean natural duration of the mucoceles was 3.63 (± 4.7; 1-24) months. After self-healing of the mucocele, the patients were followed up for 17.21 (± 9.45; 2-30) months and there were no reported recurrences. CONCLUSIONS: Lower lip mucoceles have a high potential for self-healing and patients may be routinely encouraged to wait for self-healing. CLINICAL RELEVANCE: The high self-healing rate observed in this study suggests that a conservative, non-interventional approach might be considered as the first-line management for lower lip mucoceles.

Optimization of Composite Enzymatic Extraction, Structural Characterization and Biological Activity of Soluble Dietary Fiber from Akebia trifoliata Peel.

In order to reduce the waste of Akebia trifoliata peel and maximize its utilization, in this study, on the basis of a single-factor experiment and the response surface method, the optimum technological conditions for the extraction of soluble dietary fiber from Akebia trifoliata peel with the compound enzyme method were obtained. The chemical composition, physical and chemical properties, structural characterization and biological activity of the purified soluble dietary fiber (AP-SDF) from the Akebia trifoliata peel were analyzed. We discovered that that the optimum yield was 20.87% under the conditions of cellulase addition 600 U/g, enzymolysis time 100 min, solid-liquid ratio 1:24 g/mL and enzymolysis temperature 51 °C. At the same time, AP-SDF was a porous network structure cellulose type I acidic polysaccharose mainly composed of arabinoxylan (36.03%), galacturonic acid (27.40%) and glucose (19.00%), which possessed the structural characteristic peaks of the infrared spectra of polysaccharides and the average molecular weight (Mw) was 95.52 kDa with good uniformity. In addition, the AP-SDF exhibited high oil-holding capacity (15.11 g/g), good water-holding capacity and swelling capacity, a certain antioxidant capacity in vitro, hypoglycemic activity in vitro for α-glucosidase inhibition and hypolipidemic activity in vitro for the binding ability of bile acids and cholesterol. These results will provide a theoretical basis for the development of functional products with antioxidant, hypoglycemic and hypolipidemic effects, which have certain application value in related industries.

DGK5-mediated phosphatidic acid homeostasis interplays with reactive oxygen species in plant immune signaling.

Reactive oxygen species (ROS) and phosphatidic acid (PA) are important second messengers in plant immunity. PA binding to RBOHD, an NADPH oxidase responsible for ROS production, enhances RBOHD stability and promotes ROS production. Distinct phosphorylation of the lipid kinase DGK5 optimizes the PA burst in regulating ROS production.

Phosphorylation-mediated inactivation of C3H14 by MPK4 enhances bacterial-triggered immunity in Arabidopsis.

Perception of pathogen-associated molecular patterns (PAMPs) triggers mitogen-activated protein (MAP) kinase 4 (MPK4)-mediated phosphorylation and induces downstream transcriptional reprogramming, but the mechanisms of the MPK4 defense pathway are poorly understood. Here, we showed that phosphorylation-mediated inactivation of the CCCH protein C3H14 by MPK4 positively regulates the immune response in Arabidopsis (Arabidopsis thaliana). Compared with wild-type plants, loss-of-function mutations in C3H14 and its paralog C3H15 resulted in enhanced defense against Pst DC3000 in infected leaves and the development of systemic acquired resistance (SAR), whereas C3H14 or C3H15 overexpression enhanced susceptibility to this pathogen and failed to induce SAR. The functions of C3H14 in PAMP-triggered immunity (PTI) and SAR were dependent on MPK4-mediated phosphorylation. Challenge with Pst DC3000 or the flagellin peptide flg22 enhanced the phosphorylation of C3H14 by MPK4 in the cytoplasm, relieving C3H14-inhibited expression of PTI-related genes and attenuating C3H14-activated expression of its targets NIM1-INTERACTING1 (NIMIN1) and NIMIN2, two negative regulators of SAR. Salicylic acid (SA) affected the MPK4-C3H14-NIMIN1/2 cascades in immunity, but SA signaling mediated by the C3H14-NIMIN1/2 cascades was independent of MPK4 phosphorylation. Our study suggests that C3H14 might be a negative component of the MPK4 defense signaling pathway.

The CCCH zinc finger protein C3H15 negatively regulates cell elongation by inhibiting brassinosteroid signaling.

Plant CCCH proteins participate in the control of multiple developmental and adaptive processes, but the regulatory mechanisms underlying these processes are not well known. In this study, we showed that the Arabidopsis (Arabidopsis thaliana) CCCH protein C3H15 negatively regulates cell elongation by inhibiting brassinosteroid (BR) signaling. Genetic and biochemical evidence showed that C3H15 functions downstream of the receptor BR INSENSITIVE 1 (BRI1) as a negative regulator in the BR pathway. C3H15 is phosphorylated by the GLYCOGEN SYNTHASE KINASE 3 -like kinase BR-INSENSITIVE 2 (BIN2) at Ser111 in the cytoplasm in the absence of BRs. Upon BR perception, C3H15 transcription is enhanced, and the phosphorylation of C3H15 by BIN2 is reduced. The dephosphorylated C3H15 protein accumulates in the nucleus, where C3H15 regulates transcription via G-rich elements (typically GGGAGA). C3H15 and BRASSINAZOLE RESISTANT 1 (BZR1)/BRI1-EMS-SUPPRESSOR 1 (BES1), two central transcriptional regulators of BR signaling, directly suppress each other and share a number of BR-responsive target genes. Moreover, C3H15 antagonizes BZR1 and BES1 to regulate the expression of their shared cell elongation-associated target gene, SMALL AUXIN-UP RNA 15 (SAUR15). This study demonstrates that C3H15-mediated BR signaling may be parallel to, or even attenuate, the dominant BZR1 and BES1 signaling pathways to control cell elongation. This finding expands our understanding of the regulatory mechanisms underlying BR-induced cell elongation in plants.

Metastasis-directed treatment in kidney cancer.

PURPOSE OF REVIEW: To provide a critical overview of the latest evidence on the role of metastasis-direct treatment (MDT) in the management of metastatic renal cell carcinoma (mRCC). RECENT FINDINGS: This is a nonsystematic review of the English language literature published since January 2021. A PubMed/MEDLINE search using various search terms was conducted, including only original studies. After title and abstract screening, selected articles were grouped into two main areas which mirror the main treatment options in this setting: surgical metastasectomy (MS) and stereotactic radiotherapy (SRT). While a limited number of retrospective studies have been reported on surgical MS, the consensus of these reports is that extirpation of metastasis should be part of a multimodal management strategy for carefully selected cases. In contrast, there have been both retrospective studies and a small number of prospective studies on the use of SRT of metastatic sites. SUMMARY: As the management of mRCC rapidly evolves, and evidence on MDT - both in the form of MS and SRT - has continued to build over the past 2 years. Overall, there is growing interest in this therapeutic option, which is increasingly being implemented and seems to be safe and potentially beneficial in well selected disease scenarios.

The safety and immunogenicity of inactivated COVID-19 vaccine in old pulmonary tuberculosis patients.

The immunogenicity and safety of vaccines against coronavirus disease 2019 (COVID-19) remain unknown in patients with a history of pulmonary tuberculosis (OPTB). Therefore, the safety and effectiveness of inactivated vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were assessed in patients with a history of PTB. The study cohort included 106 healthy controls and 93 adult patients with OPTB who received a two-dose vaccination. The study period was 21 to 105 days. Concentrations of antibodies (Abs) against receptor-binding domain (RBD) IgG and SARS-CoV-2 neutralizing Abs (NAbs) were measured, in addition to the frequencies of SARS-CoV-2-specific B and a portion T cells. The incidence of adverse events was similar between the OPTB patients and healthy controls. No severe adverse events occurred. Concentrations of Abs against RBD-IgG and CoV-2 neutralizing Abs in addition to the frequencies of RBD-specific memory B cells proportions were lower in OPTB patients than the healthy controls (all, p < 0.05), while the frequencies of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4+) cells were higher (p = 0.023). There was no obvious correlation between age and blood concentrations of Abs against RBD-IgG and CoV-2 neutralizing Abs, while immune responses were similar in the fibrosis and calcification groups. The period of time following full-course vaccination and lymphocyte counts were associated to anti-RBD-IgG responses. Inactivated COVID-19 vaccinations were well tolerated in OPTB patients, although immunogenicity was limited in this population. This study has been registered at ClinicalTrials.gov (NCT05043246).

Neoadjuvant pazopanib in nonrhabdomyosarcoma soft tissue sarcomas (ARST1321): A report of major wound complications from the Children's Oncology Group and NRG Oncology.

BACKGROUND AND OBJECTIVES: The impact upon wound healing of targeted molecular therapies, when incorporated into neoadjuvant therapy of soft tissue sarcoma, is largely unknown. Here, we describe wound complications following addition of pazopanib, a tyrosine kinase inhibitor (TKI), to neoadjuvant radiotherapy (RT) +/- chemotherapy for soft tissue sarcoma. METHODS: Wound complications were evaluated on dose-finding and randomized arms of ARST1321, a phase II/III study incorporating neoadjuvant RT, +/- pazopanib, +/- ifosfamide/doxorubicin (ID) for sarcoma therapy. RESULTS: Of 85 evaluable patients, 35 (41%) experienced postoperative wound complications. Most (57%) were grade III. Randomization to pazopanib + RT + ID carried a 50% wound complication rate (17/34, with 47% grade III), compared to 22% (5/23) with ID + RT alone. In nonchemotherapy study arms, pazopanib + RT resulted in a 59% wound complication rate versus 25% for those receiving RT alone. Grade III wound complications occurred among 26% (15/58) of all patients receiving pazopanib. Wound complications occurred a median of 35 days postoperatively. Some occurred following diagnostic biopsies and at remote surgical sites. CONCLUSION: The addition of pazopanib to neoadjuvant chemotherapy and RT resulted in a higher wound complication rate following therapy of soft tissue sarcoma. The rate of grade III complications remained comparable to that reported in contemporary literature.

Cognitive deficits after general anaesthesia in animal models: a scoping review.

BACKGROUND: It remains controversial whether general anaesthetic drugs contribute to perioperative neurocognitive disorders in adult patients. Preclinical studies have generated conflicting results, likely because of differing animal models, study protocols, and measured outcomes. This scoping review of preclinical studies addressed the question: 'Do general anaesthetic drugs cause cognitive deficits in adult animals that persist after the drugs have been eliminated from the brain?' METHODS: Reports of preclinical studies in the MEDLINE database published from 1953 to 2021 were examined. A structured review process was used to assess original studies of cognitive behaviours, which were measured after treatment (≥24 h) with commonly used general anaesthetic drugs in adult animals. RESULTS: The initial search yielded 380 articles, of which 106 were fully analysed. The most frequently studied animal model was male (81%; n=86/106) rodents (n=106/106) between 2-3 months or 18-20 months of age. Volatile anaesthetic drugs were more frequently studied than injected drugs, and common outcomes were memory behaviours assessed using the Morris water maze and fear conditioning assays. Cognitive deficits were detected in 77% of studies (n=82/106) and were more frequent in studies of older animals (89%), after inhaled anaesthetics, and longer drug treatments. Limitations of the studies included a lack of physiological monitoring, mortality data, and risk of bias attributable to the absence of randomisation and blinding. CONCLUSIONS: Most studies reported cognitive deficits after general anaesthesia, with age, use of volatile anaesthetic drugs, and duration of anaesthesia as risk factors. Recommendations to improve study design and guide future research are presented.

The Impact of Inflammation and General Anesthesia on Memory and Executive Function in Mice.

BACKGROUND: Perioperative neurocognitive disorders (PNDs) are complex, multifactorial conditions that are associated with poor long-term outcomes. Inflammation and exposure to general anesthetic drugs are likely contributing factors; however, the relative impact of each factor alone versus the combination of these factors remains poorly understood. The goal of this study was to compare the relative impact of inflammation, general anesthesia, and the combination of both factors on memory and executive function. METHODS: To induce neuroinflammation at the time of exposure to an anesthetic drug, adult male mice were treated with lipopolysaccharide (LPS) or vehicle. One day later, they were anesthetized with etomidate (or vehicle). Levels of proinflammatory cytokines were measured in the hippocampus and cortex 24 hours after LPS treatment. Recognition memory and executive function were assessed starting 24 hours after anesthesia using the novel object recognition assay and the puzzle box, respectively. Data are expressed as mean (or median) differences (95% confidence interval). RESULTS: LPS induced neuroinflammation, as indicated by elevated levels of proinflammatory cytokines, including interleukin-1ß (LPS versus control, hippocampus: 3.49 pg/mg [2.06-4.92], P < .001; cortex: 2.60 pg/mg [0.83-4.40], P = .010) and tumor necrosis factor-α (hippocampus: 3.50 pg/mg [0.83-11.82], P = .002; cortex: 2.38 pg/mg [0.44-4.31], P = .021). Recognition memory was impaired in mice treated with LPS, as evinced by a lack of preference for the novel object (novel versus familiar: 1.03 seconds [-1.25 to 3.30], P = .689), but not in mice treated with etomidate alone (novel versus familiar: 2.38 seconds [0.15-4.60], P = .031). Mice cotreated with both LPS and etomidate also exhibited memory deficits (novel versus familiar: 1.40 seconds [-0.83 to 3.62], P = .383). In the puzzle box, mice treated with either LPS or etomidate alone showed no deficits. However, the combination of LPS and etomidate caused deficits in problem-solving tasks (door open task: -0.21 seconds [-0.40 to -0.01], P = .037; plug task: -0.30 seconds [-0.50 to -0.10], P < .001; log values versus control), indicating impaired executive function. CONCLUSIONS: Impairments in recognition memory were driven by inflammation. Deficits in executive function were only observed in mice cotreated with LPS and etomidate. Thus, an interplay between inflammation and etomidate anesthesia led to cognitive deficits that were not observed with either factor alone. These findings suggest that inflammation and anesthetic drugs may interact synergistically, or their combination may unmask covert or latent deficits induced by each factor alone, leading to PNDs.

Optical detection using CRISPR-Cas12a of Helicobacter pylori for veterinary applications.

Helicobacter pylori (H. pylori) is a zoonotic gastric microorganism capable of efficient interspecies transmission. Domesticated companion animals, particularly dogs and cats, serve as natural reservoirs for H. pylori. This phenomenon facilitates the extensive dissemination of H. pylori among households with pets. Hence, the prompt and precise identification of H. pylori in companion animals holds paramount importance for the well-being of both animals and their owners. With the assistance of Multienzyme Isothermal Rapid Amplification (MIRA) and CRISPR-Cas12a system, we successfully crafted a highly adaptable optical detection platform for H. pylori. Three sensor systems with corresponding visual interpretations were proposed. This study demonstrated a rapid turnaround time of approximately 45 min from DNA extraction to the result display. Moreover, this platform topped germiculture and real-time PCR in terms of sensitivity or efficiency in clinical diagnoses of 66 samples. This platform possesses significant potential as a versatile approach and represents the premiere application of CRISPR for the non-invasive detection of H. pylori in companion animals, thereby mitigating the dissemination of H. pylori among household members.

Fine-tuning brassinosteroid biosynthesis via 3'UTR-dependent decay of CPD mRNA modulates wood formation in Populus.

Brassinosteroids (BRs) are plant hormones that regulate wood formation in trees. Currently, little is known about the post-transcriptional regulation of BR synthesis. Here, we show that during wood formation, fine-tuning BR synthesis requires 3'UTR-dependent decay of Populus CONSTITUTIVE PHOTOMORPHOGENIC DWARF 1 (PdCPD1). Overexpression of PdCPD1 or its 3' UTR fragment resulted in a significant increase of BR levels and inhibited secondary growth. In contrast, transgenic poplars repressing PdCPD1 3' UTR expression displayed moderate levels of BR and promoted wood formation. We show that the Populus GLYCINE-RICH RNA-BINDING PROTEIN 1 (PdGRP1) directly binds to a GU-rich element in 3' UTR of PdCPD1, leading to its mRNA decay. We thus provide a post-transcriptional mechanism underlying BRs synthesis during wood formation, which may be useful for genetic manipulation of wood biomass in trees.

PagERF81 regulates lignin biosynthesis and xylem cell differentiation in poplar.

Lignin is a major component of plant cell walls and is essential for plant growth and development. Lignin biosynthesis is controlled by a hierarchical regulatory network involving multiple transcription factors. In this study, we showed that the gene encoding an APETALA 2/ethylene-responsive element binding factor (AP2/ERF) transcription factor, PagERF81, from poplar 84 K (Populus alba × P. glandulosa) is highly expressed in expanding secondary xylem cells. Two independent homozygous Pagerf81 mutant lines created by gene editing, produced significantly more but smaller vessel cells and longer fiber cells with more lignin in cell walls, while PagERF81 overexpression lines had less lignin, compared to non-transgenic controls. Transcriptome and reverse transcription quantitative PCR data revealed that multiple lignin biosynthesis genes including Cinnamoyl CoA reductase 1 (PagCCR1), Cinnamyl alcohol dehydrogenase 6 (PagCAD6), and 4-Coumarate-CoA ligase-like 9 (Pag4CLL9) were up-regulated in Pagerf81 mutants, but down-regulated in PagERF81 overexpression lines. In addition, a transient transactivation assay revealed that PagERF81 repressed the transcription of these three genes. Furthermore, yeast one hybrid and electrophoretic mobility shift assays showed that PagERF81 directly bound to a GCC sequence in the PagCCR1 promoter. No known vessel or fiber cell differentiation related genes were differentially expressed, so the smaller vessel cells and longer fiber cells observed in the Pagerf81 lines might be caused by abnormal lignin deposition in the secondary cell walls. This study provides insight into the regulation of lignin biosynthesis, and a molecular tool to engineer wood with high lignin content, which would contribute to the lignin-related chemical industry and carbon sequestration.

Hepatic venous gas secondary to pulmonary barotrauma: rat model study.

Intrahepatic gas (IHG) is commonly observed during early postmortem examinations of humans with upper or lower airway obstructions. We conducted a study to test the hypothesis that intrapulmonary gas could retrogradely spread to the hepatic vein following pulmonary barotrauma (PB). To establish a rat model of pulmonary barotrauma, we utilized a controllable pressure-vacuum pump to apply airway pressure (40, 60, or 80 mmHg). The rats were dissected directly at the end of the experiment, and histological analysis was performed through microscopic examination of the rats. Additionally, the rats were ventilated with meglumine diatrizoate under pressures of 160 and 250 mmHg to observe the signal dynamic diffusion using X-ray fluoroscopy examination. Rats exhibited classical changes associated with PB, such as alveolar rupture, pulmonary interstitial emphysema, and hemorrhage, as well as IHG characterized by the presence of gas in the hepatic vein and hepatic sinusoids. Air emboli were not observed in the liver in any of the 40 mmHg groups. However, they were observed in the liver in the 60 and 80 mmHg groups, the amount and size of air emboli in the 80 mmHg group were greater than those in the 60 mmHg group (p < 0.05). The 80 mmHg group presented radial grape-like bubbles in the centrilobular portion of the liver accompanied by congestion in the peripheral region of the hepatic lobule. X-ray fluoroscopy examination revealed a gradual enhancement of dynamic contrast medium signals from the lung to the inferior vena cava and then to the liver. Our findings indicate that pulmonary barotrauma can lead to the retrograde spread of intrapulmonary gas to the hepatic vein. When it is clear that no decomposition of the body has occurred, the presence of IHG serves as a novel indicator for the diagnosis of obstructive pulmonary disease or obstruction in the upper or lower airway.

[Effects and mechanisms of total flavones of Abelmoschus manihot in inhibiting podocyte necroptosis and renal fibrosis in diabetic kidney disease].

Previous studies have shown that high blood glucose-induced chronic microinflammation can cause inflammatory podocyte injury in patients with diabetic kidney disease(DKD). Therein, necroptosis is a new form of podocyte death that is closely associated with renal fibrosis(RF). To explore the effects and mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese herbal medicine Abelmoschus manihot for treating kidney diseases, on podocyte necroptosis and RF in DKD, and to further reveal its scientific connotation with multi-pathway and multi-target, the authors randomly divided all rats into four groups: a namely normal group, a model group, a TFA group and a rapamycin(RAP) group. After the modified DKD rat models were successfully established, four group rats were given double-distilled water, TFA suspension and RAP suspension, respectively by gavage every day. At the end of the 4th week of drug treatment, all rats were sacrificed, and the samples of their urine, blood and kidneys were collected. And then, the various indicators related to podocyte necroptosis and RF in the DKD model rats were observed, detected and analyzed, respectively. The results indicated that, general condition, body weight(BW), serum creatinine(Scr), urinary albumin(UAlb), and kidney hypertrophy index(KHI) in these modified DKD model rats were both improved by TFA and RAP. Indicators of RF, including glomerular histomorphological characteristics, fibronectin(FN) and collagen type Ⅰ(collagen Ⅰ) staining extent in glomeruli, as well as the protein expression levels of FN, collagen Ⅰ, transforming growth factor-ß1(TGF-ß1) and Smad2/3 in the kidneys were improved respectively by TFA and RAP. Podocyte damage, including foot process form and the protein expression levels of podocin and CD2AP in the kidneys was improved by TFA and RAP. In addition, tumor necrosis factor-α(TNF-α)-mediated podocyte necroptosis in the kidneys, including the morphological characteristics of podocyte necroptosis, the extent and levels of the protein expression of TNF-α and phosphorylated mixed lineage kinase domain like pseudokinase(p-MLKL) was improved respectively by TFA and RAP. Among them, RAP had the better effect on p-MLKL. More importantly, the activation of the receptor interacting serine/threonine protein kinase 1(RIPK1)/RIPK3/MLKL signaling axis in the kidneys, including the expression levels of its key signaling molecules, such as phosphorylated receptor interacting serine/threonine protein kinase 1(p-RIPK1), p-RIPK3, p-MLKL and cysteinyl aspartate specific proteinase-8(caspase-8) was improved respectively by TFA and RAP. Among them, the effect of TFA on p-RIPK1 was superior. On the whole, in this study, the authors demonstrated that TFA alleviates podocyte necroptosis and RF in DKD through inhibiting the activation of the TNF-α-mediated RIPK1/RIPK3/MLKL signaling axis in diabetic kidneys. The authors' findings provide new pharmacological evidence to reveal the scientific connotation of TFA in treating RF in DKD in more depth.

TCOF1 coordinates oncogenic activation and rRNA production and promotes tumorigenesis in HCC.

Treacle ribosome biogenesis factor 1 (TCOF1) is a nucleolar factor that regulates ribosomal DNA (rDNA) transcription in the nucleolus. TCOF1 has been previously reported to be implicated in Treacher Collins-Franceschetti syndrome (TCS), a congenital disorder of craniofacial development. Except TCS, TCOF1 has not been reported to be involved in other diseases so far. Here, we show that TCOF1 expression is aberrantly elevated in human hepatocellular carcinoma (HCC) and correlates with HCC progression and poor outcome. In vitro and in vivo studies reveal oncogenic roles of TCOF1 in HCC. Mechanistically, TCOF1 regulates KRAS-activated genes and epithelial-mesenchymal transition (EMT) genes in HCC and is required for the increased ribosomal RNA (rRNA) production, a hallmark of cancer. Interestingly, our analysis reveals an inverse correlation between TCOF1 expression and tumor infiltration of antitumor immune cells, suggesting that TCOF1 may also have an important impact on antitumor immune responses in HCC. Together, our findings support a model in which TCOF1 coordinates oncogenic activation and rRNA production to promote HCC tumorigenesis. The inverse correlation between TCOF1 expression and the infiltration of antitumor immune cells opens a new avenue to understanding the promoting role of TCOF in HCC tumorigenesis.