Characterizing flavor development in low-salt Chinese horse bean-chili paste through integrated metabolomics and metagenomics.

This study utilized metabolomics and metagenomics to investigate the microbial composition and functions in low- and high-salt Chinese horse bean-chili pastes (CHCPs). The results showed that 25 key metabolites were identified to distinguish the flavor attributes between the two samples. Leuconostoc was identified as the dominant microbiota in low-salt CHCP, while Pantoea prevailed in the high-salt CHCP. Compared to traditional high-salt fermentation, low-salt and inoculated fermentation promoted the increase in the relative abundances of Companionlactobacillus, Levilactobacillus, Tetragenococcus, Zygosaccharomyces and Wickerhamiella as well as the enrichment of carbohydrate and amino acid metabolic pathways, which contributed to the enhancement of characteristic flavor compounds. Further metabolic pathway reconstruction elucidated 21 potential microbial genera associated with the formation of key metabolites, such as Leuconostoc, Levilactobacillus, Pantoea, and Pectobacterium. This study may provide insights for optimizing the fermentation process and improving the flavor quality of low-salt CHCP and similar fermentation products. KEYWORDS: Low-salt fermentation Hight-salt fermentation Chinese horse-bean chili paste Flavor formation Metabolomics Metagenomics.

Temporal dynamics of immune cell patterns in bladder cancer patients receiving Bacillus Calmette-Guérin therapy.

BACKGROUND: Bacillus Calmette-Guérin (BCG) is capable of enhancing the infiltration of immune cells into the tumour. However the temporal dynamics of immune cell patterns in patients receiving BCG instillation remains unclear. METHODS: Ninety-six patients who underwent intravesical BCG therapy, comprising 46 responders and 50 non-responders, were retrospectively enroled to explore the evolving immune landscape. This study involved a detailed examination of sequential samples collected before, during, and after BCG treatment to assess BCG's influence on the immune microenvironment, employing techniques such as immunohistochemistry, fluorescent multiplex immunohistochemistry, and mass spectrometry techniques. RESULTS: Our study found that initial BCG instillation leads to enhanced immune cell infiltration, correlating with treatment efficacy, with responders exhibiting more pronounced increases. Non-responders experience a rise in immune cell infiltration and PD-L1 expression during the first instillation, which returns to baseline after treatment. In non-responders, BCG re-challenge fail to further increase immune cell infiltration into the tumour or improve patient outcomes. Strikingly, proteomics data revealed that GBP1 expression was induced by BCG treatment in non-responders. CONCLUSIONS: Our findings demonstrated the induction of tumour PD-L1 expression by BCG in non-responders, and therefore provide insights for the combination of BCG and anti-PD1/anti-PD-L1 therapy.

Study of sulfoglycolysis in Enterococcus gilvus reveals a widespread bifurcated pathway for dihydroxypropanesulfonate degradation.

Sulfoquinovose (SQ), the polar head group of sulfolipids essential for photosynthesis, is naturally abundant. Anaerobic Firmicutes degrade SQ through a transaldolase-dependent (sulfo-TAL) pathway, producing dihydroxypropanesulfonate (DHPS). Some bacteria extend this pathway by the sequential action of HpfG and HpfD converting DHPS to 3-hydroxypropanesulfonate (3-HPS) via 3-sulfopropionaldehyde (3-SPA). Here, we report a variant sulfo-TAL pathway in Enterococcus gilvus, involving additional enzymes, a NAD+-dependent 3-SPA dehydrogenase HpfX, and a 3-sulfopropionyl-CoA synthetase HpfYZ, which oxidize 3-SPA to 3-sulfopropionate (3-SP) coupled with ATP formation. E. gilvus grown on SQ or DHPS produced a mixture of 3-HPS and 3-SP, indicating the bifurcated pathway. Similar genes are found in various Firmicutes, including gut bacteria. Importantly, 3-SP, but not 3-HPS, can serve as a respiratory terminal electron acceptor for Bilophila wadsworthia, a common intestinal pathobiont, resulting in the production of toxic H2S. This research expands our understanding of sulfonate metabolism and reveals cross-feeding in the anaerobic microbiome.

Herbal medicines for SOD1G93A mice of amyotrophic lateral sclerosis: preclinical evidence and possible immunologic mechanism.

Currently, there is no cure or effective treatment for Amyotrophic Lateral Sclerosis (ALS). The mechanisms underlying ALS remain unclear, with immunological factors potentially playing a significant role. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), a systematic review of preclinical studies was conducted, searching seven databases including PubMed, covering literature from the inception of the databases to April 10, 2024. Methodological quality of the included literature was assessed using CAMARADES, while the risk of bias in the included studies was evaluated using SYRCLE's ROB tool. Review Manager 5.4.1 statistical software was used for meta-analysis of the outcomes. The scoping review followed the Joanna Briggs Institute Methodological Guidelines and reporting of this review followed the PRISMA-extension for Scoping Reviews (PRISMA -ScR) checklist to explore the immunological mechanisms of Herbal Medicine (HM) in treating ALS. This systematic review and meta-analysis involved 18 studies with a total of 443 animals. The studies scored between 4 to 8 for methodological quality and 3 to 7 for risk of bias, both summing up to 10.A remarkable effects of HM in ALS mice, including onset time(Standardized Mean Difference(SMD): 1.75, 95% Confidence Interval(CI) (1.14 ~ 2.36), Z = 5.60, P < 0.01), survival time(SMD = 1.42, 95% CI (0.79 ~ 2.04), Z = 4.44, P < 0.01), stride length(SMD=1.90, 95% CI (1.21 to 2.59), Z = 5.39, P < 0.01) and duration time (Mean Difference(MD)=6.79, 95% CI [-0.28, 13.87], Z=1.88, P =0.06), showing HM's certain efficiency in treating ALS mice. The scoping review ultimately included 35 articles for review. HMs may treat ALS through mechanisms such as combating oxidative stress, excitatory amino acid toxicity, and calcium cytotoxicity, understanding and exploring the mechanisms will bring hope to patients. Individual herbs and their formulations within HM address ALS through a variety of immune pathways, including safeguarding the blood-brain barrier, countering neuroinflammation, impeding complement system activation, mitigating natural killer cell toxicity, and regulating T cell-mediated immune pathways. The preclinical evidence supports the utilization of HM as a conventional treatment for ALS mice. Growing evidence indicates that HM may potentially delay neurological degeneration in ALS by activating diverse signaling pathways, especially immune pathways.

NIR-II Anti-Stokes Luminescence Nanocrystals with 1710 nm Excitation for in vivo Bioimaging.

Anti-Stokes luminescence (ASL) based on lanthanide nanocrystals holds immense promise for in vivo optical imaging and bio-detection, which benefits from filtered autofluorescence. However, the current longest emission and excitation wavelengths of lanthanide ASL system were shorter than 1200 nm and 1532 nm, respectively, which limited tissue penetration depth and caused low signal-to-noise ratio (SNR) of in vivo imaging due to tissue scattering and water absorption. In this work, we extended the excitation wavelength to 1710 nm with the second near-infrared (NIR-II, 1000-1700 nm) emission up to 1650 nm through a novel ASL nanocrystal LiYF4:10%Tm@LiYF4:70%Er@LiYF4. Compared with 1532 nm excited ASL nanoprobes, the 1710 nm excited nanocrystals could improve in vivo imaging SNR by 12.72 folds. Based on this excellent imaging performance of the proposed ASL nanoprobes, three-channel in vivo dynamic multiplexed imaging was achieved, which quantitatively revealed metabolic rates of intestinal dynamics and liver enrichment under anesthetized and awake states. This innovative ASL nanoprobes and dynamic multiplexed imaging technology would be conducive to optimizing dosing regimen and treatment plans across various physiological conditions.

Disproportionality analysis of the safety profile of rufinamide in the real world: an evaluation of the FDA Adverse Event Reporting System database.

BACKGROUND: Rufinamide (RUF) is an antiepileptic drug recently introduced for managing seizures in Lennox-Gastaut syndrome (LGS), but its adverse reactions are not well understood. This study aims to evaluate RUF's safety profile using data from the FDA Adverse Event Reporting System (FAERS). METHODS: Disproportionality analysis was conducted to assess RUF-associated adverse drug events (ADEs), using reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma-Poisson shrinker (MGPS). RESULTS: We collected 338 ADE reports related to RUF. Nervous system disorders were the most frequently reported signals, and several new ADEs were detected, including atonic seizures, sudden unexplained death in epilepsy, seizure clusters, multi-drug resistance, and Stevens-Johnson syndrome. Nearly half of the ADEs in pediatric patients were psychological or neurological. Disproportionality analysis within 4 weeks of treatment showed high RORs for QT shortening, sudden death, and atonic seizures. CONCLUSIONS: Our study revealed prospective signals of new ADEs linked to RUF as well as revealed that both prescribers and patients were more conscious of the risks involved in its clinical use.

Expression and clinical significance of SYNE3 in non-small cell lung cancer.

OBJECTIVE: To detect the expression of Spectrin Repeat Containing Nuclear Envelope Family Member 3 (SYNE3) and Cluster of Differentiation 34 (CD34) in non-small cell lung cancer (NSCLC). It also aimed to explore the relationship between SYNE3 and NSCLC angiogenesis and clinicopathologic features to identify new biomarkers for NSCLC. METHODS: Forty-five NSCLC stage IA-IVB tissue specimens from patients diagnosed at Bazhong Central Hospital were collected from January to September 2022, along with 45 para-cancerous normal lung tissues as controls. None of the NSCLC patients had received anti-tumor therapies, including radiotherapy, chemotherapy, targeted therapy, immunotherapy, or traditional Chinese medicine. All specimens were stained for SYNE3 and CD34 using the Streptavidin-Peroxidase (SP) method. The expression levels of SYNE3 and CD34 in NSCLC tissues and para-cancerous tissues were detected, and a correlation analysis between SYNE3 and clinicopathological features was performed. The number of CD34-labeled microvessels was counted using the Microvessel density (MVD) method. The relationship between SYNE3 and NSCLC angiogenesis was examined through the correlation between CD34-MVD and NSCLC clinicopathologic features. RESULTS: The expression of SYNE3 in NSCLC was significantly lower than that in para-cancerous normal lung tissues, while the expression of CD34 in NSCLC was significantly higher than in para-cancerous normal lung tissues (P=0.037). SYNE3 expression in NSCLC was negatively correlated with tumor diameter and was lower in male patients with a smoking history compared to female patients without a smoking history. CD34 expression was positively correlated with Tumor, Node, Metastasis staging and lymph node metastasis. There was a significant correlation between the expression of SYNE3 and CD34 in NSCLC (r=0.450, P=0.000). CONCLUSION: SYNE3 was lowly expressed and negatively correlated with tumor size in NSCLC, whereas CD34 was highly expressed and positively correlated with TNM stage and lymph node metastasis. The significant correlation between the expressions of SYNE3 and CD34 suggests that SYNE3 may play a key role in NSCLC angiogenesis and progression.

Association of critical hypoperfusion biomarkers on CT with futile recanalization and poor outcome after mechanical thrombectomy in acute ischemic stroke.

BACKGROUND AND PURPOSE: We aimed to investigate the association between critical perfusion delay and poor outcome among recanalized stroke patients with anterior large-vessel occlusion, and to use pretreatment hypoperfusion biomarkers on CT to predict futile recanalization even after successful thrombectomy. METHODS: An ischemic region with time-to-maximum (Tmax) > 12s-10s was defined as critical hypoperfusion, Tmax > 8s as moderate hypoperfusion, and hypoperfusion intensity ratio (HIR, volumetric ratio of Tmax > 10s / Tmax > 6s) represented for severity of critical hypoperfusion and rCBF < 30% for ischemic core. The associations between these CT perfusion characteristics and favorable or unfavorable outcome (mRS 0-2 versus 3-6) were analyzed in univariable regression, and a multivariable model was then used to predict futile recanalization. RESULTS: Seventy-nine stroke patients were included and had good grades of instant recanalization. Forty-two patients (53%) had poor outcomes, and they had a significantly larger volume of critical hypoperfusion as seen with Tmax > 10s and > 12s (P = 0.032 and 0.008, respectively), a larger volume of ischemic core (P = 0.011) and a higher HIR (P = 0.002) than those patients achieving good outcomes. In the univariable analysis, a lower HIR (OR, 0.008; 95%CI, 0.001-0.254, P = 0.006) was associated with favorable outcome. The volume size of Tmax > 12s was significantly and positively correlated with the size of ischemic core. A HIR value higher than 0.491 might predict a futile recanalization and poor outcome (AUC = 0.701). CONCLUSIONS: The critical hypoperfusion biomarkers on CTP could be useful in triaging endovascular treatment and identifying stroke patients at risk of futile recanalization.

Association between human herpes simplex virus and severe headache or migraine among aged 20-49 years: a cross-sectional study.

Background and purpose: Previous studies have shown that human herpes simplex virus (HSV) infection may be associated with the onset of headache or migraine. We aimed to investigate the association between HSV infection and severe headache or migraine. Materials and methods: The cross-sectional data on 5,730 participants aged 20-49 years were obtained from the 1999-2004 National Health and Nutrition Examination Survey (NHANES). We used weighted logistic regression analysis to assess the association between HSV infection (HSV-1 gG-1 and HSV-2 gG-2) and severe headache or migraine, and performed subgroup analyses. Results: Our study found that women, higher education, higher body mass index, better family conditions, smoking and alcohol consumption were all associated with severe headaches or migraines. After adjusting for confounding factors such as sex, age, race, and education, HSV-2 (+) was still significantly associated with severe headache or migraine (OR = 1.22, 95%CI:1.03-1.46, p = 0.0443). In subgroup analyses, we found that participants with HSV-1 (-) and HSV-2 (+) were also significantly associated with severe headache or migraine (OR = 1.41, 95%CI:1.04-1.91, p = 0.0281). Conclusion: HSV-2 gG-2(+) was significantly associated with severe headache or migraine.

Particulate matter induced cognitive impairments via endoplasmic reticulum stress-mediated damage to mitochondria-associated endoplasmic reticulum membranes in immature rats.

Particulate matter (PM) exposure has been increasingly recognized as detrimental to cognitive function and is associated with neurodevelopmental disorders. Mitochondria-associated endoplasmic reticulum membranes (MAMs) form an integrated interface between mitochondria and the endoplasmic reticulum (ER), facilitating crucial cellular functions. Prolonged ER stress (ERS) is implicated in various pathological states in the nervous system. MAMs and ERS may play vital roles in adverse effects of early-life PM exposure on cognitive abilities. This study investigated whether ERS plays a role in PM-induced MAMs dysfunction, leading to neuronal damage and cognitive impairments in early postnatal rats. Using a rat model with PM exposure concentrations of 2 and 10 mg/kg from postnatal Day 3 (PND3) to PND28, we observed that PM exposure resulted in anxiety-like behavior and impaired spatial working memory. The protein levels of ERS markers, including GRP78 and CHOP, were significantly increased in response to PM exposure. Western blot, transmission electron microscopy (TEM), and immunofluorescence analyses revealed decreased MAMs-related proteins and disrupted MAM structure and function caused by PM exposure. Administration of the ERS inhibitor 4-phenylbutyric acid (4-PBA) ameliorated these effects, restoring MAMs integrity and improving cognitive deficits. These findings highlighted the key role of ERS-MAMs dysfunction in PM-induced neurotoxicity and cognitive impairments, providing a new perspective and strategy for the prevention of cognitive deficits in early age with PM exposure.

Halogen-Bond-Assisted NHC-Catalyzed (Dynamic) Kinetic Resolution for the Atroposelective Synthesis of Heterobiaryls.

We report a novel halogen-bond-assisted NHC-catalyzed (dynamic) kinetic resolution strategy for the synthesis of axially chiral heterobiaryls. A class of axially chiral quinolines are prepared efficiently in excellent enantioselectivities (≤98% ee) employing 3-5 mol % NHC catalyst. Mechanistic studies reveal the indispensability of 5-bromo-2-iodobenzaldehyde in this reaction, in which a pivotal halogen bonding interaction plays a crucial role in the process.

The association between FLAIR vascular hyperintensities and outcomes in patients with border zone infarcts treated with medical therapy may vary with the infarct subtype.

RATIONALE AND OBJECTIVES: Fluid-attenuated inversion recovery vessel hyperintensities (FVHs) reflect the haemodynamic state and may aid in predicting the prognosis of border zone (BZ) infarct patients. This study was to explore the relationship between FVHs and functional outcomes for different BZ infarct subtypes following medical therapy administration. MATERIALS AND METHODS: Consecutive patients with ischemic stroke were retrospectively enrolled and classified into internal BZ (IBZ) infarct, cortical BZ (CBZ) infarct and mixed-type infarct patients. FVHs were quantified using the FVH-Alberta Stroke Program Early CT Score (ASPECTS) system, and the scores were used to divide the patients into low-FVH (0-3) and high-FVH (4-7) groups. The FVH location and the cerebrovascular stenotic degree were recorded. Logistic regression was performed to identify risk factors for poor outcomes (modified Rankin scale score ≥3). RESULTS: A total of 207 BZ infarct patients (IBZ, n = 130; CBZ, n = 52; mixed-type, n = 25) were included. The FVH score was positively correlated with cerebrovascular stenosis (r = 0.332, P < 0.001) in all patients. A high FVH score was associated with poor outcomes in all (OR 2.568, 95% CI (1.147 to 5.753), P = 0.022) and in CBZ infarct patients (OR 9.258, 95% CI 1.113 to 77.035), P = 0.040). FVH-diffusion-weighted imaging (DWI) mismatch was not significantly associated with outcomes in the entire patient group or in any subgroup. CONCLUSIONS: A high FVH score is associated with poor long-term outcomes in patients with CBZ infarcts but not in those with IBZ or mixed-type infarcts.

A deep learning approach for deriving wheat phenology from near-surface RGB image series using spatiotemporal fusion.

Accurate monitoring of wheat phenological stages is essential for effective crop management and informed agricultural decision-making. Traditional methods often rely on labour-intensive field surveys, which are prone to subjective bias and limited temporal resolution. To address these challenges, this study explores the potential of near-surface cameras combined with an advanced deep-learning approach to derive wheat phenological stages from high-quality, real-time RGB image series. Three deep learning models based on three different spatiotemporal feature fusion methods, namely sequential fusion, synchronous fusion, and parallel fusion, were constructed and evaluated for deriving wheat phenological stages with these near-surface RGB image series. Moreover, the impact of different image resolutions, capture perspectives, and model training strategies on the performance of deep learning models was also investigated. The results indicate that the model using the sequential fusion method is optimal, with an overall accuracy (OA) of 0.935, a mean absolute error (MAE) of 0.069, F1-score (F1) of 0.936, and kappa coefficients (Kappa) of 0.924 in wheat phenological stages. Besides, the enhanced image resolution of 512 × 512 pixels and a suitable image capture perspective, specifically a sensor viewing angle of 40° to 60° vertically, introduce more effective features for phenological stage detection, thereby enhancing the model's accuracy. Furthermore, concerning the model training, applying a two-step fine-tuning strategy will also enhance the model's robustness to random variations in perspective. This research introduces an innovative approach for real-time phenological stage detection and provides a solid foundation for precision agriculture. By accurately deriving critical phenological stages, the methodology developed in this study supports the optimization of crop management practices, which may result in improved resource efficiency and sustainability across diverse agricultural settings. The implications of this work extend beyond wheat, offering a scalable solution that can be adapted to monitor other crops, thereby contributing to more efficient and sustainable agricultural systems.

Association Between Changes in Preoperative Serum Creatinine and Acute Kidney Injury After Cardiac Surgery: A Retrospective Cohort Study.

INTRODUCTION: Limited information exists regarding the impact of preoperative serum creatinine changes on cardiac surgery-associated acute kidney injury (CSA-AKI). This study aimed to investigate the development of AKI in patients with a baseline estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m2 who present with an elevation in preoperative serum creatinine. METHODS: This retrospective cohort study assessed patients who underwent open-heart surgery. Preoperative serum creatinine change was calculated as the ratio of the maximum preoperative serum creatinine value to the baseline creatinine (MCR). Patients were categorized into three groups based on MCR: non-elevation (≤1.0), mild elevation (1.0 to 1.5), and pronounced elevation (≥1.5). Multivariable logistic regression was used to estimate the risk of AKI, severe AKI, and non-recovery from AKI. RESULTS: There were significant increases in the odds of AKI (adjusted odds ratio [OR], 1.42; 95% confidence interval [CI], 1.29-1.57; per 0.1 increase in MCR), severe AKI (adjusted OR, 1.28; 95% CI, 1.15-1.41), and AKI non-recovery (adjusted OR, 1.29; 95% CI, 1.16-1.43). Pronounced elevation in preoperative serum creatinine was associated with a higher risk of AKI (adjusted OR, 15.45; 95% CI, 6.63-36.00), severe AKI (adjusted OR, 3.62; 95% CI, 1.20-10.87), and AKI non-recovery (adjusted OR, 4.74; 95% CI, 1.63-13.89) than non-elevation. Mild elevation in preoperative serum creatinine was also significantly associated with AKI (adjusted OR, 3.76; 95% CI, 1.92-7.37). CONCLUSIONS: Elevation in preoperative serum creatinine from baseline was associated with an increased risk of AKI; even mild elevation significantly increased the risk of AKI.

Clinical application of n-butyl-2- cyanoacrylate（NBCA） in the transarterial embolization for type I/II endoleak during and after EVAR surgery.

OBJECTIVE: Exploring the effectiveness and safety of n-butyl-2-cyanoacrylate (NBCA) in the transarterial embolization for common endoleak during and after endovascular repair of aortic aneurysm (EVAR). METHODS: A total of 226 patients with abdominal aortic aneurysm (AAA) were treated with EVAR in 4 years August 2019 to February 2023, including 46 patients with ruptured aneurysms (rAAA). Account 37 cases developed endoleak during EVAR surgery and follow-up period, 28 non-ruptured AAA patients and 9 rAAA patients, then treated with NBCA for transarterial embolization. Follow up for at least six months to observe its clinical efficacy and adverse reactions. RESULTS: Among 37 cases of endoleak, there were eight cases of primary type Ia endoleak and one cases of primary right type Ib endoleak in the rAAA group, one case of primary type Ib endoleak, two cases of secondary type Ia endoleak and 25 cases of Postoperative type II endoleak in the non-ruptured AAA group. Three patients with primary type Ia endoleak were treated with coil assisted NBCA in the rAAA group, while the remaining 34 patients with type I and type II endoleaks were treated with NBCA alone. All transarterial embolization achieved technical success and the endoleak disappeared. Postoperative hospitalization observation showed that three cases patients in the rAAA group who experienced primary type Ia endoleak during emergency EVAR surgery died within 4 days after surgery due to hemorrhagic shock and multiple organ failure. Two patients experienced non-AAA related deaths during the follow-up period. CONCLUSION: Transartrial embolization with NBCA for the treatment of primary and secondary endoleak is a safe and effective method. It can achieve more dense embolization of the aneurysm sac and more complex endoleaks embolization. And it showed a low recurrence rate of endoleak and the incidence of perioperative complications after surgery, which is worthy of clinical promotion and application. Even in emergency EVAR combined with primary type I endoleak treatment in rAAA patients, patients can still benefit.

Protective Effects of Baicalein on Lipopolysaccharide-Induced AR42J PACs through Attenuation of Both Inflammation and Pyroptosis via Downregulation of miR-224-5p/PARP1.

Background: Baicalein has been used to treat inflammation-related diseases; nevertheless, its specific mechanism of action is unclear. Therefore, we examined the protective effects of baicalein on lipopolysaccharide-induced damage to AR42J pancreatic acinar cells (PACs) and determined its mechanism of action for protection. Methods: An in vitro cell model of acute pancreatitis (AP) was established using lipopolysaccharide (LPS) (1 mg/L)-induced PACs (AR42J), and the relative survival rate was determined using the 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) technique. Flow cytometry was applied to evaluate the apoptotic rates of AR42J PACs. The RNA and protein expression of miR-224-5p, poly ADP-ribose polymerase-1 (PARP1), nuclear transcription factor-κB65 (NF-κB65), phospho-kappa B alpha(p-IκB-α), interleukin(IL)-18R, NOD-like receptor thermal protein domain-associated protein 3 (NLRP3), gasdermin D (GSDMD), apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1 was detected based on the WB and RT-PCR assays. IL-1ß, IL-6, IL-18, and TNF-α expression levels in AR42J cells were measured via ELISA method. The cell morphology was examined using the AO/EB method. Results: The experiment confirmed a significant increase in the activity of AR42J cells treated with various doses of baicalein. Moreover, IL-1ß, IL-6, TNF-α, and IL-18 expression levels in AR42J cells were dramatically reduced (P < 0.05), while miR-224-5p level was obviously enhanced. The protein and gene expression of PARP1, NF-κB65, p-IκB-α, IL-18R, GSDMD, ASC, NLRP3, and caspase-1 was obviously decreased (P < 0.05). Apoptosis in AR42J cells was significantly reduced with significant improvement in cell morphology. Conclusion: Baicalein may significantly alleviate LPS-induced AR42J PAC damage by inhibiting the inflammatory response and pyroptosis. Its mode of action might be linked to higher miR-224-5p expression, which inhibits the PARP1/NF-κB and NLPR3/ASC/caspase-1/GSDMD pathways.

Phylogenomic analyses of the pantropical Platycerium Desv. (Platycerioideae) reveal their complex evolution and historical biogeography.

Platycerium is a genus of pantropical epiphytic ferns consisting of ca. 18 species and are highly sought after by horticultural enthusiasts. Although the monophyly of this genus has been well supported in previous molecular studies, as an intercontinentally disjunct genus, the origin and distribution pattern of Platycerium were elusive and controversial. This is mainly due to limited taxon sampling, a plastid representing only a single coalescent history, the lack of fossil evidence, and so on. Here, by utilizing genome-skimming sequencing, transcriptome sequencing, and flow cytometry, we integrated chloroplast genomes, data of single-copy nuclear genes, ploidy levels, morphology, and geographic distribution to understand the species phylogeny and the evolutionary and biogeographic history of Platycerium. Our major results include: (1) based on both plastid and nuclear datasets, Platycerium is consistently resolved into three fully supported clades: the Afro-American (AA) clade, the Javan-Australian (JA) clade, and the Malayan-Asian (MA) clade. The AA clade and MA clade are further divided into three and two subclades, respectively; (2) a large amount of gene tree conflict, as well as cytonuclear discordance, was found and can be explained by hybridization and incomplete lineage sorting, and most of the hybridization hypotheses represented ancient hybridization events; (3) through molecular dating, the crown age of Platycerium is determined to be at approximately 32.79 Ma based on the plastid dataset or 29.08 Ma based on the nuclear dataset in the Middle Oligocene; (4) ancestral area reconstruction analysis from different datasets showed that Platycerium most likely originated from Indochina; (5) current distribution patterns are resultant from long-distance dispersals, ancient orogeny, and an ancient climate event; and (6) species diversification was driven by polyploidization, dispersal, and hybridization. This study presented here will help understand the evolution of tropical plant flora and provide a reference for the cultivation and breeding of staghorn ferns.

An integrative strategy used by the aphid Uroleucon formosanum to counter host sesquiterpene lactone defense: Insights from combined genomic and transcriptomic analysis.

Insect herbivores adapt and develop strategies to counteract plant chemical defenses. The aphid Uroleucon formosanum is a serious sap-sucking pest that infests lettuces containing toxic sesquiterpene lactones (STLs). Herein, we employed a combination of genome sequencing and RNA-seq transcriptome profiling to understand the mechanisms underlying phytotoxin tolerance in U. formosanum. We generated the first chromosome-level genome assembly for U. formosanum, with a total size of 453.26 Mb and a scaffold N50 of 33.22 Mb. Comparative genomic analyses revealed an enrichment of signals for positive selection and gene family expansion in immune-related pathways. Specifically, the expanded set of heat shock protein 70 (HSP70) genes showed upregulation after treatment with lactucin, suggesting that they may play a role in the immune response against STLs. The expression of takeout-like genes and cuticle-associated genes was also significantly increased in the lactucin-treated samples. Additionally, 53 cytochrome P450 monooxygenase, 30 carboxylesterase, 19 glutathione S-transferase, 32 uridine diphosphate glycosyltransferase and 63 ATP-binding cassette (ABC) transporter genes were identified in the U. formosanum genome. CYP4C1, CYP6A13 and 7 ABC genes were strongly upregulated in response to lactucin treatment, indicating the involvement of detoxifying enzymes in the tolerance of U. formosanum to STLs. Our findings suggest that the cuticle barrier, immune response and enzyme-mediated metabolic detoxification jointly enhance the tolerance of U. formosanum to phytotoxins and promote its adaptation to host plants. This study presents a valuable genomic resource and provides insights into insect adaptation to plant chemical challenges and future technological developments for pest management.

Efficacy of tissue-bone homeostasis manipulation on the gait and knee function for the patients with knee osteoarthritis: a randomized controlled trial.

BACKGROUND: Knee osteoarthritis (KOA) was characterized by pain and limited joint function, which seriously affected the quality of life of patients. The vast majority of KOA was closely related to degeneration of the patellofemoral joint and abnormal patellar movement trajectory. Tissue-bone homeostasis manipulation (TBHM) could correct abnormal patellar movement trajectory on the basis of loosening soft tissue. However, there was little strong evidence to verify its efficacy on the patients with KOA. The study objective was to explore the efficacy of the TBHM on gait and knee function in the patients with KOA. METHODS: Sixty KOA patients were randomly assigned to either the joint mobilization (n = 30) or TBHM (n = 30) group. The joint mobilization group received joint mobilization, while the TBHM group received TBHM. For two groups, the patients participated in 30 min rehabilitation sessions thrice per week for 12 weeks. The primary outcome was biomechanical gait outcomes during walking, including step length, step velocity, double support, knee range of motion (ROM), and knee adduction moment (KAM). The secondary outcomes were the Western Ontario and McMaster Index (WOMAC) and 36-Item short- form health survey (SF-36), which reflected improvements in knee function and quality of life, respectively. At baseline and 12 weeks, evaluations were conducted and compared between groups. RESULTS: After a 12-week intervention, significant group differences were observed in KAM (p = 0.018), WOMAC-Pain (p = 0.043) and WOMAC-Stiffness (p = 0.026). A noteworthy finding was the presence of a significant interaction effect between group and time specifically observed in step velocity during gait (p = 0.046), WOMAC-Function (p = 0.013) and SF-36 (p = 0.027). Further analysis revealed a significant difference in step velocity (p = 0.034), WOMAC-Function (p = 0.025) and SF-36 (p = 0.042) during post-assessment between the two groups. Moreover, a significant time effect was observed across all outcomes of the two groups (p < 0.05). CONCLUSION: The TBHM intervention has better improved the gait, knee function, and quality of life in the patients with KOA. TRIAL REGISTRATION: ITMCTR, ITMCTR2200005507. Registered 06/01/2022, http://itmctr.ccebtcm.org.cn/zh-CN/Home/ProjectView?pid=09cdadad-0aef-41ee-81bd-a8dceb63f7f5 .

WDR20 prevents hepatocellular carcinoma senescence by orchestrating the simultaneous USP12/46-mediated deubiquitination of c-Myc.

The dysfunction of the ubiquitin-proteasome system (UPS) facilitates the malignant progression of hepatocellular carcinoma (HCC). While targeting the UPS for HCC therapy has been proposed, identifying effective targets has been challenging. In this study, we conducted a focused screen of siRNA libraries targeting UPS-related WD40 repeat (WDR) proteins and found that silencing WDR20, a deubiquitinating enzyme activating factor, selectively inhibited the proliferation of HCC cells without affecting normal hepatocytes. Moreover, the downregulation of WDR20 expression induced HCC cellular senescence and suppressed tumor progression in xenograft, sleeping beauty transposon/transposase, and hydrodynamic tail vein injection-induced HCC models, and Alb-Cre+/MYC+ HCC transgenic mouse models. Mechanistically, we found that WDR20 silencing disturbed the protein stability of c-Myc, orchestrating the simultaneous USP12/46-mediated deubiquitination of c-Myc, thereby promoting the transcriptional activation of CDKN1A. Further investigation revealed a positive coexpression of WDR20 and c-Myc in a tissue microarray with 88 HCC clinical samples. By employing three patient-derived organoids from individuals with HCC, we have validated the decrease in c-Myc expression and the significant induction of senescence and growth inhibition following silencing of WDR20. This study not only uncovers the biological function of WDR20 and elucidates the molecular mechanism underlying its negative regulation of HCC cellular senescence but also highlight the potential of WDR20 as a promising target for HCC therapy.