An electrochemical sensor based on 2D Zn-MOFs and 2D C-Ti3C2Tx composite materials for rapid and direct detection of various foodborne pathogens.

Rapid screening for foodborne pathogens is crucial for food safety. A rapid and one-step electrochemical sensor has been developed for the detection of Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Salmonella typhimurium (S. typhimurium). Through the construction of aptamer/two-dimensional carboxylated Ti3C2Tx (2D C-Ti3C2Tx)/two-dimensional Zn-MOF (2D Zn-MOF) composites, the recognition elements, signal tags, and signal amplifiers are integrated on the electrode surface. Pathogens are selectively captured using the aptamer, which increases the impedance of the electrode surface，leads to a decrease in the 2D Zn-MOF current. Bacteria can be rapidly quantified using a one-step detection method and the replacement of aptamers. The detection limits for E. coli, S. aureus, and S. typhimurium are 6, 5, and 5 CFU·mL-1, respectively. The sensor demonstrated reliable detection capabilities in real-sample testing. Therefore, the one-step sensor based on the 2D Zn-MOF and 2D C-Ti3C2Tx has significant application value in the detection of foodborne pathogens.

Design, Synthesis, and Anticancer Activity of Novel Enmein-Type Diterpenoid Derivatives Targeting the PI3K/Akt/mTOR Signaling Pathway.

The enmein-type diterpenoids are a class of anticancer ent-Kaurane diterpnoids that have received much attention in recent years. Herein, a novel 1,14-epoxy enmein-type diterpenoid 4, was reported in this project for the first time. A series of novel enmein-type diterpenoid derivatives were also synthesized and tested for anticancer activities. Among all the derivatives, compound 7h exhibited the most significant inhibitory effect against A549 cells (IC50 = 2.16 µM), being 11.03-folds better than its parental compound 4. Additionally, 7h exhibited relatively weak anti-proliferative activity (IC50 > 100 µM) against human normal L-02 cells, suggesting that it had excellent anti-proliferative selectivity for cancer cells. Mechanism studies suggested that 7h induced G0/G1 arrest and apoptosis in A549 cells by inhibiting the PI3K/AKT/mTOR pathway. This process was associated with elevated intracellular ROS levels and collapsed MMP. In summary, these data identified 7h as a promising lead compound that warrants further investigation of its anticancer properties.

Metformin acts on miR-181a-5p/PAI-1 axis in stem cells providing new strategies for improving age-related osteogenic differentiation decline.

A general decline in the osteogenic differentiation capacity of human bone marrow mesenchymal stem cells (hBMSCs) in the elderly is a clinical consensus, with diverse opinions on the mechanisms. Many studies have demonstrated that metformin (MF) significantly protects against osteoporosis and reduces fracture risk. However, the exact mechanism of this effect remains unclear. In this study, we found that the decreased miR-181a-5p expression triggered by MF treatment plays a critical role in recovering the osteogenic ability of aging hBMSCs (derived from elderly individuals). Notably, the miR-181a-5p expression in hBMSCs was significantly decreased with prolonged MF (1000 µM) treatment. Further investigation revealed that miR-181a-5p overexpression markedly impairs the osteogenic ability of hBMSCs, while miR-181a-5p inhibition reveals the opposite result. We also found that miR-181a-5p could suppress the protein translation process of plasminogen activator inhibitor-1 (PAI-1), as evidenced by luciferase assays and western blots. Additionally, low PAI-1 levels were associated with diminished osteogenic ability, whereas high levels promoted it. These findings were further validated in human umbilical cord mesenchymal stem cells (hUCMSCs). Finally, our in vivo experiment with a bone defects rat model confirmed that the agomiR-181a-5p (long-lasting miR-181a-5p mimic) undermined bone defects recovery, while the antagomiR-181a-5p (long-lasting miR-181a-5p inhibitor) significantly promoted the bone defects recovery. In conclusion, we found that MF promotes bone tissue regeneration through the miR-181a-5p/PAI-1 axis by affecting MSC osteogenic ability, providing new strategies for the treatment of age-related bone regeneration disorders.

Diagnostic value of an interpretable machine learning model based on clinical ultrasound features for follicular thyroid carcinoma.

Background: Follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA) present diagnostic challenges due to overlapping clinical and ultrasound features. Improving the diagnosis of FTC can enhance patient prognosis and effectiveness in clinical management. This study seeks to develop a predictive model for FTC based on ultrasound features using machine learning (ML) algorithms and assess its diagnostic effectiveness. Methods: Patients diagnosed with FTA or FTC based on surgical pathology between January 2009 and February 2023 at Zhejiang Provincial Cancer Hospital and Zhejiang Provincial People's Hospital were retrospectively included. A total of 562 patients from Zhejiang Provincial Cancer Hospital comprised the training set, and 218 patients from Zhejiang Provincial People's Hospital constituted the validation set. Subsequently, clinical parameters and ultrasound characteristics of the patients were collected. The diagnostic parameters were analyzed using the least absolute shrinkage and selection operator and multivariate logistic regression screening methods. Next, a comparative analysis was performed using seven ML models. The area under the receiver operating characteristic (ROC) curve (AUC), accuracy, sensitivity, specificity, positive predicted value (PPV), negative predicted value (NPV), precision, recall, and comprehensive evaluation index (F-score) were calculated to compare the diagnostic efficacy among the seven models and determine the optimal model. Further, the optimal model was validated, and the SHapley Additive ExPlanations (SHAP) approach was applied to explain the significance of the model variables. Finally, an individualized risk assessment was conducted. Results: Age, echogenicity, thyroglobulin antibody (TGAb), echotexture, composition, triiodothyronine (T3), thyroglobulin (TG), margin, thyroid-stimulating hormone (TSH), calcification, and halo thickness >2 mm were influential factors for diagnosing FTC. The XGBoost model was identified as the optimal model after a comprehensive evaluation. The AUC of this model in the validation set was 0.969 [95% confidence interval (CI), 0.946-0.992], while its precision sensitivity, specificity, and accuracy were 0.791, 0.930, 0.913 and 0.917, respectively. Conclusions: XGBoost model based on ultrasound features was constructed and interpreted using the SHAP method, providing evidence for the diagnosis of FTC and guidance for the personalized treatment of patients.

Association Between Red Cell Distribution Width and Liver Injury after Cardiac and Aortic Aneurysm Surgery with Cardiopulmonary Bypass.

OBJECTIVES: This study aimed to investigate the association between preoperative red blood cell distribution width (RDW) levels and liver injury (LI) after cardiac surgery, to highlight RDW's usefulness in the early identification and intervention for patients at high risk of LI. DESIGN: A retrospective observational study. SETTING: A university-affiliated teaching hospital and tertiary referral center. PARTICIPANTS: Adult patients who underwent cardiac and aortic aneurysm surgery at Changhai Hospital in 2021. INTERVENTIONS: Postoperative LI was defined by increased liver enzyme levels and/or hyperbilirubinemia, noted from the time of surgery to discharge. Logistic regression analyses were conducted to examine the RDW-LI relationship, with stratified analyses based on age, gender, and anemia. Survival within 30 days was assessed using the Kaplan-Meier method, with survival curve differences analyzed via the log-rank test. The study included 3 sets of sensitivity analyses. MEASUREMENTS AND MAIN RESULTS: Postoperative LI was observed in 75 patients (10%). Multivariate regression analysis showed a significant association between high RDW levels and postoperative LI (adjusted odds ratio, 3.25; p = 0.033; 95% confidence intefal, 1.10-9.63), even after adjusting for all covariates. This association remained consistent across 3 sets of sensitivity analyses. Subgroup analysis showed men had a higher correlation with LI (p for interaction = 0.041). Kaplan-Meier analysis indicated a significantly lower survival rate in the LI group (76%) compared with the non-LI group (99.6%; p < 0.001). CONCLUSIONS: Preoperative RDW levels are significantly associated with postoperative LI. RDW could serve as a significant useful marker for early detection and intervention in patients at high risk of LI, thereby potentially improving patient outcomes.

The delivery of PD-L1 siRNA by neutrophil-targeted lipid nanoparticles effectively ameliorates sepsis.

BACKGROUND: Sepsis, a complex and life-threatening disease, poses a significant global burden affecting over 48 million individuals. Recently, it has been reported that programmed death-ligand 1 (PD-L1) expressed on neutrophils is involved in both inflammatory organ dysfunction and immunoparalysis in sepsis. However, there is a dearth of strategies to specifically target PD-L1 in neutrophils in vivo. METHODS: We successfully developed two lipid nanoparticles (LNPs) specifically targeting neutrophils by delivering PD-L1 siRNA via neutrophil-specific antibodies and polypeptides. In vivo and in vitro experiments were performed to detect lipid nanoparticles into neutrophils. A mouse cecal ligation and puncture (CLP) model was used to detect neutrophil migration, neutrophil extracellular traps (NETs) level, and organ damage. RESULT: The PD-L1 siRNA-loaded LNPs that target neutrophils suppressed inflammation, reduced the release of NETs, and inhibited T-lymphocyte apoptosis. This approach could help maintain homeostasis of both the immune and inflammatory responses during sepsis. Furthermore, the PD-L1 siRNA-loaded LNPs targeting neutrophils have the potential to ameliorate the multi-organ damage and lethality resulting from CLP. CONCLUSIONS: Taken together, our data identify a previously unknown drug delivery strategy targeting neutrophils, which represents a novel, safe, and effective approach to sepsis therapy.

Use of peroral cholangiopancreatoscopy-assisted endoscopic mucosal resection for biliopancreatic intraductal lesions.

BACKGROUND AND STUDY AIM: This study aimed to assess the feasibility and safety of performing cholangiopancreatoscopy-assisted endoscopic mucosal resection (CA-EMR) for biliopancreatic intraductal lesions. PATIENTS AND METHODS: Special electrocautery snares and injection needles that can pass through the working channel of a single-operator cholangiopancreatoscope (SOC) were developed. Between November 2023 and April 2024, we performed CA-EMR for 2 patients with gallbladder polyps, 1 patient a neoplastic lesion in the common bile duct (CBD) and 1 patient with a neoplastic lesion in the main pancreatic duct (PD). The technical success rate and adverse events were recorded. RESULTS: All 4 CA-EMR procedures were performed successfully. Postoperative pathology revealed inflammatory gallbladder polyps in 2 patients, low grade intraepithelial neoplasia (LGIN) of CBD in 1 patient and intraductal papillary mucinous neoplasm (IPMN) in 1 patient. The patient with IPMN experienced mild postoperative pancreatitis and recovered after conservative treatment. No adverse events were encountered in the other 3 CA-EMR procedures. CONCLUSION: This study preliminarily confirmed the feasibility and safety of CA-EMR for treating biliopancreatic intraductal lesions.

Association of late-life blood pressure change with cerebral small vessel disease in the MIND-China study.

OBJECTIVES: This study aimed to investigate the associations between changes in blood pressure (BP) and cerebral small vessel disease (CSVD). METHODS: This study included 401 participants in the magnetic resonance imaging (MRI) sub-study conducted between 2018 and 2020 as a part of the Multidomain Interventions to Delay Dementia and Disability in Rural China project. MRI markers of CSVD were assessed based on international criteria. Individualized linear regression models evaluated changes in BP by estimating the trend of blood pressure changes over time and fitting a straight line from 2014 to 2018. The data were analyzed using logistic and general linear regression models. RESULT: The mean age of the participants was 64.48 ± 2.69 years, with 237 (59.1%) being females. Increases in systolic BP in later life were significantly associated with larger volumes of periventricular white matter hyperintensity (WMH), greater perivascular spaces in the basal ganglia (BG-PVS) burden, and the presence of deep lacunes and cerebral microbleeds. Additionally, increases in diastolic BP in later life were significantly associated with the presence of infratentorial and deep lacunes. CONCLUSIONS: CSVDs are associated with increased exposure to elevated BP later in life.

Association of enlarged perivascular spaces with cognitive function in dementia-free older adults: A population-based study.

Introduction: We sought to characterize cognitive profiles associated with enlarged perivascular spaces (EPVS) among Chinese older adults. Methods: This population-based study included 1191 dementia-free participants (age ≥60 years) in the MIND-China MRI Substudy (2018-2020). We visually evaluated EPVS in basal ganglia (BG) and centrum semiovale (CSO), white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs), and cortical superficial siderosis. We used a neuropsychological test battery to assess cognitive function. Data were analyzed using general linear models. Results: Greater BG-EPVS load was associated with lower z-scores in memory, verbal fluency, and global cognition (p < 0.05); these associations became non-significant when controlling for other cerebral small vessel disease (CSVD) markers (e.g., WMHs, lacunes, and mixed CMBs). Overall, CSO-EPVS load was not associated with cognitive z-scores (p > 0.05); among apolipoprotein E (APOE) -ε4 carriers, greater CSO-EPVS load was associated with lower verbal fluency z-score, even when controlling for other CSVD markers (p < 0.05). Discussion: The associations of BG-EPVS with poor cognitive function in older adults are largely attributable to other CSVD markers. HIGHLIGHTS: The association of enlarged perivascular spaces (EPVS) with cognitive function in older people is poorly defined.The association of basal ganglia (BG)-EPVS with poor cognition is attributed to other cerebral small vessel disease (CSVD) markers.In apolipoprotein E (APOE) ε4 carriers, a higher centrum semiovale (CSO)-EPVS load is associated with poorer verbal fluency.

Coaxial Electrospun Polycaprolactone/Gelatin Nanofiber Membrane Loaded with Salidroside and Cryptotanshinone Synergistically Promotes Vascularization and Osteogenesis.

Background: Salidroside (SAL) is the most effective component of Rhodiola rosea, a traditional Chinese medicine. Cryptotanshinone (CT) is the main fat-soluble extract of Salvia miltiorrhiza, exhibiting considerable potential for application in osteogenesis. Herein, a polycaprolactone/gelatin nanofiber membrane loaded with CT and SAL (PSGC membrane) was successfully fabricated via coaxial electrospinning and characterized. Methods and Results: This membrane capable of sustained and controlled drug release was employed in this study. Co-culturing the membrane with bone marrow mesenchymal stem cells and human umbilical vein endothelial cells revealed excellent biocompatibility and demonstrated osteogenic and angiogenic capabilities. Furthermore, drug release from the PSGC membrane activated the Wnt/ß-catenin signaling pathway and promoted osteogenic differentiation and vascularization. Evaluation of the membrane's vascularization and osteogenic capacities involved transplantation onto a rat's subcutaneous area and assessing rat cranium defects for bone regeneration, respectively. Microcomputed tomography, histological tests, immunohistochemistry, and immunofluorescence staining confirmed the membrane's outstanding angiogenic capacity two weeks post-operation, with a higher incidence of osteogenesis observed in rat cranial defects eight weeks post-surgery. Conclusion: Overall, the SAL- and CT-loaded coaxial electrospun nanofiber membrane synergistically enhances bone repair and regeneration.

The incidence, risk factors, and prognosis of acute kidney injury in patients after cardiac surgery.

Background: Acute kidney injury (AKI) represents a significant complication following cardiac surgery, associated with increased morbidity and mortality rates. Despite its clinical importance, there is a lack of universally applicable and reliable methods for the early identification and diagnosis of AKI. This study aimed to examine the incidence of AKI after cardiac surgery, identify associated risk factors, and evaluate the prognosis of patients with AKI. Method: This retrospective study included adult patients who underwent cardiac surgery at Changhai Hospital between January 7, 2021, and December 31, 2021. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Perioperative data were retrospectively obtained from electronic health records. Logistic regression analyses were used to identify independent risk factors for AKI. The 30-day survival was assessed using the Kaplan-Meier method, and differences between survival curves for different AKI severity levels were compared using the log-rank test. Results: Postoperative AKI occurred in 257 patients (29.6%), categorized as stage 1 (179 patients, 20.6%), stage 2 (39 patients, 4.5%), and stage 3 (39 patients, 4.5%). The key independent risk factors for AKI included increased mean platelet volume (MPV) and the volume of intraoperative cryoprecipitate transfusions. The 30-day mortality rate was 3.2%. Kaplan-Meier analysis showed a lower survival rate in the AKI group (89.1%) compared to the non-AKI group (100%, P < 0.001). Conclusion: AKI was notably prevalent following cardiac surgery in this study, significantly impacting survival rates. Notably, MPV and administration of cryoprecipitate may have new considerable predictive significance. Proactive identification and management of high-risk individuals are essential for reducing postoperative complications and mortality.

Exploration of the mechanism of Qinglongyi-Buguzhi drug pair in treating vitiligo based on network pharmacology, molecular docking and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: The Qinglongyi-Buguzhi herbal pair (QB) is one of commonly used herbal combinations for treating vitiligo in traditional Chinese medicine, consisting of the exocarp of the immature fruit of Juglans regia L. or Juglans mandshurica Maxim., and dried, mature fruit of Psoralea corylifolia L. However, the active components and potential mechanisms of QB in the treatment of vitiligo are still unclear. AIM OF THE STUDY: The purpose of this study is to clarify the effects and mechanisms of QB on vitiligo treatment through integration of network pharmacology and empirical examinations. MATERIALS AND METHODS: The active components and targets of QB as well as the targets linked to vitiligo were obtained from network databases. Visualization networks were constructed with Cytoscape 3.9.1. GO and KEGG enrichment analysis were conducted to investigate the possible mechanism. Molecular docking was employed to evaluate the binding affinities between the primary active ingredients of QB and essential targets of the PI3K/Akt/Nrf2 pathway. In vivo and in vitro experiments were carried out to confirm the results of network pharmacology. RESULTS: We evaluated 44 active compounds and 602 genes from QB, and 107 of these genes linked to vitiligo. GO analysis suggested QB might lessen vitiligo by regulating oxidative stress. KEGG pathway analysis indicated the PI3K/Akt pathway may be crucial for treating vitiligo. Molecular docking results demonstrated the key active ingredients of QB had good binding activity with the major targets in the PI3K/Akt/Nrf2 pathway. In vivo, QB significantly ameliorated vitiligo model mouse's skin pathologies by reducing ROS, elevating CAT and SOD levels. Western blot showed that QB increased the phosphorylation of PI3K and Akt and the expressions of Nrf2 and HO-1 in the skin. In vitro, QB reversed H2O2-induced oxidative injury of melanocytes, enhanced cell survival rate, reduced ROS level, upregulated SOD and CAT activities, and raised the content of melanin. Moreover, QB upregulated the expression levels of Akt, Nrf2, HO-1 mRNA, Akt phosphorylation, HO-1, and nuclear Nrf2 proteins, and also encouraged the nuclear translocation of Nrf2. However, LY294002 treatment significantly reversed the regulatory effect of QB on oxidative damage of melanocytes. CONCLUSIONS: This study revealed that the therapeutic effect of QB on vitiligo was achieved through multiple components, targets and pathways. Experimental investigation demonstrated that QB could improve vitiligo via reducing oxidative stress, which was probably accomplished by activating the PI3K/Akt/Nrf2 signaling pathway.

Development and validation of a diagnostic model for cerebral small vessel disease among rural older adults in China.

Objectives: Cerebral small vessel disease (CSVD) visible on MRI can be asymptomatic. We sought to develop and validate a model for detecting CSVD in rural older adults. Methods: This study included 1,192 participants in the MRI sub-study within the Multidomain Interventions to Delay Dementia and Disability in Rural China. Total sample was randomly divided into training set and validation set. MRI markers of CSVD were assessed following the international criteria, and total CSVD burden was assessed on a scale from 0 to 4. Logistic regression analyses were used to screen risk factors and develop the diagnostic model. A nomogram was used to visualize the model. Model performance was assessed using the area under the receiver-operating characteristic curve (AUC), calibration plot, and decision curve analysis. Results: The model included age, high blood pressure, white blood cell count, neutrophil-to-lymphocyte ratio (NLR), and history of cerebral infarction. The AUC was 0.71 (95% CI, 0.67-0.76) in the training set and 0.69 (95% CI, 0.63-0.76) in the validation set. The model showed high coherence between predicted and observed probabilities in both the training and validation sets. The model had higher net benefits than the strategy assuming all participants either at high risk or low risk of CSVD for probability thresholds ranging 50-90% in the training set, and 65-98% in the validation set. Conclusion: A model that integrates routine clinical factors could detect CSVD in older adults, with good discrimination and calibration. The model has implication for clinical decision-making.

Sulfoxide-containing polymers conjugated prodrug micelles with enhanced anticancer activity and reduced intestinal toxicity.

Poly(ethylene glycol) (PEG) is widely utilized as a hydrophilic coating to extend the circulation time and improve the tumor accumulation of polymeric micelles. Nonetheless, PEGylated micelles often activate complement proteins, leading to accelerated blood clearance and negatively impacting drug efficacy and safety. Here, we have crafted amphiphilic block copolymers that merge hydrophilic sulfoxide-containing polymers (psulfoxides) with the hydrophobic drug 7-ethyl-10-hydroxylcamptothecin (SN38) into drug-conjugate micelles. Our findings show that the specific variant, PMSEA-PSN38 micelles, remarkably reduce protein fouling, prolong blood circulation, and improve intratumoral accumulation, culminating in significantly increased anti-cancer efficacy compared with PEG-PSN38 counterpart. Additionally, PMSEA-PSN38 micelles effectively inhibit complement activation, mitigate leukocyte uptake, and attenuate hyperactivation of inflammatory cells, diminishing their ability to stimulate tumor metastasis and cause inflammation. As a result, PMSEA-PSN38 micelles show exceptional promise in the realm of anti-metastasis and significantly abate SN38-induced intestinal toxicity. This study underscores the promising role of psulfoxides as viable PEG substitutes in the design of polymeric micelles for efficacious anti-cancer drug delivery.

HPLC with chiral stationary phase for separation and kinetics study of aspartic acid epimerization in Peroxiredoxin 2 active site peptide.

Amino acid epimerization, a process of converting L-amino acids to D-amino acids, will lead to modification in the protein structure and, subsequently, its biological function. This modification causes no change in protein m/z and may be overlooked during protein analysis. Aspartic Acid Epimerization (AAE) is faster than other amino acids and could be accelerated by free radicals and peroxides. In this work, a novel and site-specific HPLC method using a chiral stationary phase for determining the AAE in the active site model peptide (AP) of Peroxiredoxin 2 has been developed and validated. The developed method showed good linearity (1 - 200 µg/mL) and recoveries of the limit of quantification (LOQ), low, medium, and high concentrations were between 85% and 115%. The Kinetics of AAE in AP were studied using the developed method, and the results showed that when ascorbic acid and Cu2+ coexisted, the AP epimerized rapidly. The AAE extent increased with time and was positively correlated with hydrogen peroxide generation.

FAM3D regulation of head and neck squamous cell carcinoma behaviour through the EMT pathway.

OBJECTIVES: Head and neck squamous cell carcinoma present challenges in effective treatment, with 50%-60% of cases exhibiting recurrence or metastasis, often resistant to surgery alone. Immunotherapy, a promising approach, does not guarantee benefits for all patients. Thus, the imperative lies in identifying reliable biomarkers for predicting immunotherapy efficacy. FAM3D, a protein-coding gene known for its potent chemotactic activity in human peripheral blood monocytes and neutrophils, plays a crucial role in regulating tumour immune responses and holds promise as an immune biomarker. MATERIALS AND METHODS: We employed comprehensive database analysis to scrutinise FAM3D, evaluating its gene expression, mutation profiles and prognostic implications in head and neck squamous cell carcinoma, along with its associations with clinical characteristics and immune cell infiltration. Complementary functional experiments were conducted to delve into the potential mechanisms governed by FAM3D. RESULTS: Our findings establish a significant correlation between low FAM3D expression and the invasiveness and metastatic potential of head and neck squamous cell carcinoma. FAM3D likely exerts its influence through the regulation of epithelial-mesenchymal transition. CONCLUSIONS: FAM3D emerges as a valuable biomarker for predicting the responsiveness of patients with head and neck squamous cell carcinoma to immunotherapy, holding substantial clinical diagnostic and therapeutic relevance.

Distinct patterns of monocular advantage for facial emotions in social anxiety.

Individuals with social anxiety often exhibit atypical processing of facial expressions. Previous research in social anxiety has primarily emphasized cognitive bias associated with face processing and the corresponding abnormalities in cortico-limbic circuitry, yet whether social anxiety influences early perceptual processing of emotional faces remains largely unknown. We used a psychophysical method to investigate the monocular advantage for face perception (i.e., face stimuli are better recognized when presented to the same eye compared to different eyes), an effect that is indicative of early, subcortical processing of face stimuli. We compared the monocular advantage for different emotional expressions (neutral, angry and sad) in three groups (N = 24 per group): individuals clinically diagnosed with social anxiety disorder (SAD), individuals with high social anxiety in subclinical populations (SSA), and a healthy control (HC) group of individuals matched for age and gender. Compared to SSA and HC groups, we found that individuals with SAD exhibited a greater monocular advantage when processing neutral and sad faces. While the magnitudes of monocular advantages were similar across three groups when processing angry faces, individuals with SAD performed better in this condition when the faces were presented to different eye. The former findings suggest that social anxiety leads to an enhanced role of subcortical structures in processing nonthreatening expressions. The latter findings, on the other hand, likely reflect an enhanced cortical processing of threatening expressions in SAD group. These distinct patterns of monocular advantage indicate that social anxiety altered representation of emotional faces at various stages of information processing, starting at an early stage of the visual system.

Unveiling the Role of RNA Recognition Motif Proteins in Orchestrating Nucleotide-Binding Site and Leucine-Rich Repeat Protein Gene Pairs and Chloroplast Immunity Pathways: Insights into Plant Defense Mechanisms.

In plants, nucleotide-binding site and leucine-rich repeat proteins (NLRs) play pivotal roles in effector-triggered immunity (ETI). However, the precise mechanisms underlying NLR-mediated disease resistance remain elusive. Previous studies have demonstrated that the NLR gene pair Pik-H4 confers resistance to rice blast disease by interacting with the transcription factor OsBIHD1, consequently leading to the upregulation of hormone pathways. In the present study, we identified an RNA recognition motif (RRM) protein, OsRRM2, which interacted with Pik1-H4 and Pik2-H4 in vesicles and chloroplasts. OsRRM2 exhibited a modest influence on Pik-H4-mediated rice blast resistance by upregulating resistance genes and genes associated with chloroplast immunity. Moreover, the RNA-binding sequence of OsRRM2 was elucidated using systematic evolution of ligands by exponential enrichment. Transcriptome analysis further indicated that OsRRM2 promoted RNA editing of the chloroplastic gene ndhB. Collectively, our findings uncovered a chloroplastic RRM protein that facilitated the translocation of the NLR gene pair and modulated chloroplast immunity, thereby bridging the gap between ETI and chloroplast immunity.

Unveiling intratumoral microbiota: An emerging force for colorectal cancer diagnosis and therapy.

Microbes, including bacteria, viruses, fungi, and other eukaryotic organisms, are commonly present in multiple organs of the human body and contribute significantly to both physiological and pathological processes. Nowadays, the development of sequencing technology has revealed the presence and composition of the intratumoral microbiota, which includes Fusobacterium, Bifidobacteria, and Bacteroides, and has shed light on the significant involvement in the progression of colorectal cancer (CRC). Here, we summarized the current understanding of the intratumoral microbiota in CRC and outline the potential translational and clinical applications in the diagnosis, prevention, and treatment of CRC. We focused on reviewing the development of microbial therapies targeting the intratumoral microbiota to improve the efficacy and safety of chemotherapy and immunotherapy for CRC and to identify biomarkers for the diagnosis and prognosis of CRC. Finally, we emphasized the obstacles and potential solutions to translating the knowledge of the intratumoral microbiota into clinical practice.