Anemia, blood cell indices, genetic correlations, and brain structures: A comprehensive analysis of roles in Parkinson's disease risk.

INTRODUCTION: Anemia may contribute significantly to the onset of Parkinson's disease (PD). Current research on the association between anemia and PD risk is inconclusive, and the relationships between anemia-related blood cell indices and PD incidence require further clarification. This study aims to investigate the relationships between anemia, blood cell indicators, and PD risk using a thorough prospective cohort study. METHODS: We used data from the UK Biobank, a prospective cohort study of 502,649 participants, and ultimately, 365,982 participants were included in the analysis. Cox proportional hazards models were utilized to adjust for confounding factors, aiming to thoroughly explore the associations between anemia and blood cell indices with the risk of incident PD. The interaction between anemia and Polygenic Risk Score (PRS) for PD was also examined. Linear regression and mediation analyses assessed potential mechanisms driven by brain structures, including grey matter volume. RESULTS: During a median follow-up of 14.24 years, 2513 participants were diagnosed with PD. Anemia considerably increased PD risk (hazard ratio [HR] 1.98, 95 % confidence interval [CI]: 1.81-2.18, P < 0.001) after adjustments. Those with high PRS for anemia had an 83 % higher PD incidence compared to low PRS participants. Sensitivity analyses confirmed result robustness. Linear regression showed that anemia correlated with grey matter volumes and most white matter tracts. Furthermore, mediation analyses identified that the volume of grey matter in Thalamus mediates the relationship between anemia and PD risk. CONCLUSION: In summary, we consider there to be a substantial correlation between anemia and increased PD risk.

A natural acylphloroglucinol exerts anti-erythroleukemia effects via targeting STAT3 and p38-MAPK, and inhibiting PI3K/AKT/mTOR signaling pathway.

Erythroleukemia, a subtype of acute myeloid leukemia (AML), is a life-threatening malignancy that affects the blood and bone marrow. Despite the availability of clinical treatments, the complex pathogenesis of the disease and the severe side effects of chemotherapy continue to impede therapeutic progress in leukemia. In this study, we investigated the antitumor activity of L76, an acylphloroglucinol compound derived from Callistemon salignus DC., against erythroleukemia, along with its underlying mechanisms. MTT assays were performed to evaluate the inhibitory effects of L76 on cancer cell viability, while flow cytometry was used to analyze apoptosis and cell cycle arrest in HEL cells. The molecular mechanisms of L76 were further explored using Western blotting, microscopic analysis, and cellular thermal shift assays (CETSA). Our in vitro experiments demonstrated that L76 inhibits proliferation, induces G1/S cell cycle arrest, and promotes apoptosis in human leukemia cells. Mechanistically, L76 exerts its effects by targeting STAT3 and p38-MAPK, and by inhibiting the PI3K/AKT/mTOR signaling pathway. In conclusion, this study highlights the potential of L76 as an anti-erythroleukemia agent, demonstrating its ability to target STAT3 and p38-MAPK, and to inhibit the PI3K/AKT/mTOR signaling pathway. These findings suggest that L76 could be a promising candidate for the treatment of erythroleukemia.

Quantitative changes in platelet count in response to different pathogens: an analysis of patients with sepsis in both retrospective and prospective cohorts.

BACKGROUND: Thrombocytopenia is commonly observed in patients with sepsis and is an independent risk factor for poor prognosis. However, the changes of platelet count caused by different pathogens can vary significantly. Our study aims to evaluate the quantitative changes in platelet count in response to various pathogens. MATERIAL AND METHODS: We retrospectively analysed data of 3044 patients with sepsis from Medical Information Mart for Intensive Care (MIMIC, 2008-2019) database and prospectively collected data of 364 patients with sepsis from our local cohort of the Shandong Bloodstream Infection and Sepsis Collaboration Study (SBISC, 2020-2022). Propensity score matching (PSM) was employed to control for baseline differences in variables, except for the causative pathogen. RESULTS: Multivariate logistic analyses of both original and PSM populations identified Candida, Escherichia, Klebsiella, and Serratia species posing a higher risk for thrombocytopenia compared to others. Restricted cubic spline (RCS) curves showed L- or U-shaped associations between platelet count and 28-mortality with various cut-off values among different pathogens: ranging from 96 × 109/L in Candida species - 190 × 109/L in Klebsiella species. CONCLUSION: Our present findings indicate a pathogen-specific effect on platelet count, highlighting the importance of monitoring thrombocytopenia in patients infected with above microorganisms. Clinicians need to consider pathogen-specific thresholds when intervene on platelet count.

This study validated the differential incidence of thrombocytopenia among various pathogens within two distinct populations.Candida, Escherichia, Klebsiella, and Serratia species were identified as having a notably higher risk of causing thrombocytopenia compared to other pathogens.We observed L- or U-shaped relationships between platelet counts and 28-day mortality in Candida species, Enterococcus species, Escherichia species, Enterobacter species, Staphylococcus species, and Klebsiella species with platelet count cutoff values of 96 × 10⁹/L, 100 × 10⁹/L, 100 × 10⁹/L, 146 × 10⁹/L, 152 × 10⁹/L, and 190 × 10⁹/L, respectively.

Reduction in the risk of contrast-induced nephropathy using enhanced external counter-pulsation in patients with chronic kidney disease.

OBJECTIVE: To evaluate the efficacy of EECP in the prevention of contrast-induced nephropathy (CIN) in patients with chronic kidney disease (CKD). METHODS: A prospective trial was undertaken in the participants. A total of 280 patients with an estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m2 who underwent percutaneous coronary artery procedures were enrolled and divided into two groups: the control group (n = 100) and the EECP group (n = 180). All patients received extracellular fluid volume expansion therapy with 0.9% normal saline, and patients in the EECP groups were also treated with EECP. The renal function indexes of the two groups were determined 48-72 h after coronary artery procedures. RESULTS: In the EECP group, the BUN and serum creatinine (Scr) after coronary artery procedures were significantly lower than those before coronary artery procedures (BUN: 8.4 ± 3.5 vs. 6.6 ± 2.7 mmol/L, p < 0.001; Scr: 151.9 ± 44.7 vs. 144.5 ± 48.3 µmol/L, p < 0.001), while the eGFR was significantly increased (43.6 ± 11.4 vs. 47.1 ± 13.9 ml/min/1.73 m2, p < 0.001). The degree of Scr elevation was lower in the EECP group than in the control group (12.4 ± 15.0 vs. 20.9 ± 24.8 µmol/L, p = 0.026). Additionally, the EECP group had a lower incidence of post-procedures Scr elevation than the control group (36.5 vs. 48.0%, p = 0.042), a higher incidence of post-procedures eGFR elevation (62.2 vs. 48.0%, p = 0.021), and a lower risk of CIN (1.1 vs. 6.0%, p = 0.019). CONCLUSION: EECP therapy has a protective effect on renal function and can reduce the risk of CIN in patients with CKD.

Functional carbon nanodots enhance tomato tolerance to zinc deficient soils: Mechanisms and structure-function relationships.

Zinc (Zn) deficiency is a global problem disorder affecting both crops and humans. Herein, modified functional carbon nanodots (MFCNs) with various structures and characteristics were developed to regulate tomato yields and Zn migration in plant-soil systems affected by Zn deficiency through structure-function relationships. Sulfur-doped FCNs (S-FCNs), nitrogen-doped FCNs (N-FCNs), and nitrogen­sulfur co-doped FCNs (N,S-FCNs) were hydrothermally modified using FCNs as precursors. Their regulatory effects on tomatoes growing in Zn-deficient alkaline soils were studied in pot culture experiments. Specifically, 8 mg kg-1 of FCNs and S-FCNs improved tomato yields by 132 % and 108 %, respectively, compared with the control. However, N-FCNs and N,S-FCNs showed no significant effect on yield compared with the control (P < 0.05). Moreover, the application of FCNs or S-FCNs significantly improved fruit quality and nutritional value, including Zn content (by 26.3 % and 22.0 %, respectively) and naturally occurring antioxidants (by 3.37- and 2.08-fold for lycopene, 1.31- and 1.18-fold for flavonoids, and 2.28- and 1.89-fold for phenolics, respectively; P < 0.05). Although N-FCNs and N,S-FCNs increased Zn contents, they inhibited the synthesis of naturally occurring antioxidants in fruits. Zn bioaccessibility, uptake, and transportation in plant-soil systems were regulated by MFCNs through both direct and indirect mechanisms, including ionic reactions, plant physiology, and environmental effects. MFCNs regulated plant tolerance to Zn deficiency not only by affecting root activity, redox homeostasis, micronutrient balance, chelator synthesis, genetic expression, and plant photosynthesis but also by influencing rhizosphere soil properties and the microbial environment. Based on their dual role as "plant growth regulators" and "soil conditioners", MFCNs may have general applicability in agriculture. This study highlights the behavior of MFCNs in plant-soil systems, providing innovative nanotools for enhancing Zn availability, crop stress resistance and environmental preservation in sustainable agriculture.

Regulation of warming on the mixed decomposition of Artemisia ordosica and Leymus secalinus litter in Mu Us Desert, China is time-dependent.

Warming drives material cycling in terrestrial ecosystems by affecting litter decomposition, as it can alter litter yield, quality and decomposer composition and activity. The effect of warming on the decomposition of mixed litter in arid and semi-arid zones remains unknown. We investigated the mass loss and nutrient release dynamics during 450 days of decomposition of Artemisia ordosica, Leymus secalinus, and their mixture in Mu Us Desert by open-top chambers and litter bags. The results showed interspecific differences in the responses to warming, in that warming promoted mass loss and N and P release from L. secalinus and inhibited mass loss and P but promoting N release from A. ordosica. Mixing of A. ordosica and L. secalinus litter inhibited decomposition. Warming enhanced the antagonistic effects of mixed decomposition. The total mass loss of mixed litter was decreased by 9%, and the release of N and P was decreased by 4.9% and 12.6%, respectively. The antagonistic effects of mixed litter mass loss and P release under the warming treatment gradually strengthened with time, with N release changing from a synergistic to an antagonistic effect at 150 d. The non-additive effects produced by the mixed decomposition of A. ordosica and L. secalinus litter were jointly regulated by temperature and time. Future research on mixed litter decomposition should consider the interaction between temperature and time.

High-grade endometrial stromal sarcoma with BCOR rearrangements: clinicopathological analysis of five cases and literature reviews - an extension in understanding of morphological characteristics.

Five cases of FISH verified BCOR rearranged high-grade endometrial stromal sarcoma were retrospectively analyzed. The patient age ranged from 33 to 65 years (median, 48.4 years). Most patients presented with irregular vaginal bleeding (3/5) and uterus mass (2/5). Only one patient developed an abdominal wall metastasis and other patients remained in good condition during the follow-up. Pathological findings revealed that the tumors exhibited morphological diversity in terms of cell shape, arrangement pattern and tumor stroma, compared to previous summarized histology of BCOR rearranged high-grade endometrial stromal sarcoma. Detailed description of such morphology changes expanded our understanding of the histology of BCOR rearranged high-grade endometrial stromal sarcoma. Due to the non-specificity of morphology in such malignancies, molecular testing is needed for confirmation in all patients.

Pulmonary abscess caused by Streptococcus pseudopneumoniae in a child: A case report and review of literature.

BACKGROUND: Lung abscess found on chest X-ray and computed tomography examinations is rare in infants and young children. Several pathogens can cause lung abscesses, with the most common pathogens being anaerobes, Streptococci and Staphylococcus aureus. Streptococcus pseudopneumoniae (S. pseudopneumoniae) is a member of the Streptococcaceae family, and is mainly isolated from respiratory tract specimens. There are currently no cases of lung abscess caused by S. pseudopneumoniae in the literature. CASE SUMMARY: A 2-year-old boy was admitted to hospital due to persistent cough and fever. Lung computed tomography examination suggested the formation of a lung abscess. His diagnosis was not confirmed by testing for serum respiratory pathogens (6 items), respiratory pathogen nucleic acid (27 items), and laboratory culture. Finally, metagenomic next-generation sequencing of bronchoalveolar lavage fluid revealed the presence of S. pseudopneumoniae, confirming its role in causing the lung abscess. After receiving antibiotic treatment, reexamination with lung computed tomography showed that the abscess was resorbed and the patient's outcome was good. CONCLUSION: This is the first report of a lung abscess in a child caused by S. pseudopneumoniae infection. Metagenomic next-generation sequencing of bronchoalveolar lavage fluid is helpful in achieving rapid and accurate pathogen identification.

CT-based radiomic consensus clustering association with tumor biological behavior in clinical stage IA adenocarcinoma: a retrospective study.

Background: Research has demonstrated that radiomics models are capable of forecasting the characteristics of lung cancer. Nevertheless, due to radiomics' poor interpretability, its applicability in clinical settings remains restricted. This investigation sought to verify the correlation between radiomics features (RFs) and the biological behavior of clinical stage IA adenocarcinomas. Methods: A retrospective analysis was conducted on patients diagnosed with clinical stage IA lung adenocarcinoma who underwent resection between May 2005 and December 2018. Detailed radiomics examination of the primary tumor was carried out utilizing preoperative computed tomography (CT) images. Subsequently, patients were grouped based on their RFs using consensus clustering, enabling comparison of tumor biological characteristics among the clusters. Survival disparities among the clusters were evaluated through Kaplan-Meier and Cox analyses. Results: A consensus cluster analysis was performed on 669 patients [median age, 58 years; interquartile range (IQR), 50-64 years, 257 males, 412 females], and three distinct clusters were identified. Cluster 2 was associated with radiological solid adenocarcinoma [119 of 324 (36.7%), P<0.001], larger tumors with median tumor size of 2.1 cm with IQR of 1.7 to 2.5 cm (P<0.001), central tumor [91 of 324 (28.1%), P=0.002], pleural invasion [87 of 324 (26.9%), P<0.001], occult lymph node metastasis (ONM) [106 of 324 (32.7%), P<0.001], and a higher frequency of metastasis or recurrence [62 of 324 (19.1%), P<0.001]. The frequency of histological grade 3 was the highest in Cluster 3 [8 of 34 (23.5%), P<0.001]. Cluster 1 was associated with pure ground glass nodules (pGGNs) [184 of 310 (59.4%), P<0.001], smaller tumors with median tumor size of 1.1 cm with IQR of 0.8 to 1.4 cm (P<0.001), no pleural invasion [276 of 310 (89.0%), P<0.001], histological grade 1 [114 of 248 (46.0%), P<0.001], ONM negative [292 of 310 (94.2%), P<0.001], and a lower rate of metastasis or recurrence [298 of 310 (96.1%), P<0.001]. Conclusions: Differences in tumor biological behavior were detected among consensus clusters based on the RFs of clinical stage IA adenocarcinoma.

Exploring the role of interleukin-6 receptor blockade in epilepsy and associated neuropsychiatric conditions through a mendelian randomization study.

BACKGROUND: The interplay between inflammation, immune dysregulation, and the onset of neurological disorders, including epilepsy, has become increasingly recognized. Interleukin (IL)-6, a pro-inflammatory cytokine, is suspected to not only mediate traditional inflammatory pathways but also contribute to neuroinflammatory responses that could underpin neuropsychiatric symptoms and broader psychiatric disorders in epilepsy patients. The role of IL-6 receptor (IL6R) blockade presents an intriguing target for therapeutic intervention due to its potential to attenuate these processes. AIM: To explore the potential of IL6R blockade in reducing the risk of epilepsy and investigate whether this pathway might also influence associated psychiatric and neuropsychiatric conditions due to neuroinflammation. METHODS: Mendelian randomization (MR) analysis employing single nucleotide polymorphisms (SNPs) in the vicinity of the IL6R gene (total individuals = 408225) was used to evaluate the putative causal relationship between IL6R blockade and epilepsy (total cases/controls = 12891/312803), focal epilepsy (cases/controls = 7526/399290), and generalized epilepsy (cases/controls = 1413/399287). SNP weights were determined by their effect on C-reactive protein (CRP) levels and integrated using inverse variance-weighted meta-analysis as surrogates for IL6R effects. To address potential outlier and pleiotropic influences, sensitivity analyses were conducted employing a variety of MR methods under different modeling assumptions. RESULTS: The genetic simulation targeting IL6R blockade revealed a modest but significant reduction in overall epilepsy risk [inverse variance weighting: Odds ratio (OR): 0.827; 95% confidence interval (CI): 0.685-1.000; P = 0.05]. Subtype analysis showed variability, with no significant effect observed in generalized, focal, or specific childhood and juvenile epilepsy forms. Beyond the primary inflammatory marker CRP, the findings also suggested potential non-inflammatory pathways mediated by IL-6 signaling contributing to the neurobiological landscape of epilepsy, hinting at possible links to neuroinflammation, psychiatric symptoms, and associated mental disorders. CONCLUSION: The investigation underscored a tentative causal relationship between IL6R blockade and decreased epilepsy incidence, likely mediated via complex neuroinflammatory pathways. These results encouraged further in-depth studies involving larger cohorts and multifaceted psychiatric assessments to corroborate these findings and more thoroughly delineate the neuro-psychiatric implications of IL-6 signaling in epilepsy. The exploration of IL6R blockade could herald a novel therapeutic avenue not just for seizure management but also for addressing the broader psychiatric and cognitive disturbances often associated with epilepsy.

Lung adenocarcinoma metastatic to the ovary: a retrospective clinicopathological analysis of 17 cases and literature review.

Lung adenocarcinoma metastatic to the ovary is rarely detected in clinical practice, and only a few cases have been reported. Its clinicopathological features, molecular genetics, and prognosis have not been well characterised. The data of 17 patients diagnosed with this disease between 2013 and 2022 were analysed retrospectively. All patients were non-smokers, with a median age of 46 years (range 30-71 years). Unilateral ovarian involvement was more frequent than bilateral involvement (58.8% vs 41.2%). Lesions presented as solid ovarian or mixed cystic and solid masses, and nearly two-thirds of the tumours (11/17, 64.7%) had a diameter greater than 10 cm. Solid adenocarcinoma was the most common histological subtype (9/17, 52.9%), and three of the cases showed abundant intracellular mucin and signet ring cells. Acinar adenocarcinoma was the second most common type (6/17, 35.3%), usually of moderate to poor differentiation. The remaining two cases were identified as micropapillary adenocarcinoma and mucinous adenocarcinoma. Multinodular growth, necrosis, and lymphovascular invasion were observed in half of the cases, and most of them had a marked stromal response. The most prevalent molecular alteration was ALK-rearranged (8/17, 47.1%), followed by EGFR gene mutations (5/17, 29.4%). A total of 34 cases, comprising 17 from the cohort and 17 from the literature, were included in the survival analysis. Patients with ALK-rearranged genes demonstrated an 80.0% 2-year overall survival rate, whereas those without ALK rearrangement exhibited a lower rate of 33.7%. Although there appears to be a potentially better prognosis for patients with ALK-rearranged genes, further cases and an extended follow-up period are necessary to substantiate this observation.

Real time precisely tracing the fluctuations of mitochondrial SO2 in cells during ferroptosis and tissues using a mitochondrial-immobilized ratiometric fluorescent probe.

Mitochondrial sulfur dioxide (SO2) plays important roles in physiological and pathological activities. Unfortunately, it is lack of a reliable tool to precisely visualize the mitochondrial SO2 and elaborate its complicated functions in various cytoactivities. Here we report a mitochondrial-immobilized fluorescent probe PM-Cl consisting of coumarin and benzyl chloride modified benzothiazole, which enables selective visualization of mitochondrial SO2via chemical immobilization. The spectral results demonstrated that probe PM-Cl could respond to SO2 with high selectivity and sensitivity. Co-localization and the fluorescence of cytolysis extraction verified the excellent mitochondrial targeting and anchoring abilities. Due to the chemical immobilization, probe PM-Cl could firmly retain into mitochondria after stimulation of carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and H2O2. Significantly, a series of fluorescence images are indicative of capability for detecting the fluctuations of SO2 in mitochondria during ferroptosis. Furthermore, PM-Cl also could visualize SO2 in myocardium and muscle tissues after the stimulation of CCCP. Taken together, probe PM-Cl is a very potential molecular tool for precisely detecting mitochondrial SO2 to explore its complex functions in physiological and pathological activities.

IVF laboratory management through workflow-based RFID tag witnessing and real-time information entry.

BACKGROUND: Dual-person inspection in IVF laboratories cannot fully avoid mix-ups or embryo transfer errors, and data transcription or entry is time-consuming and redundant, often leading to delays in completing medical records. METHODS: This study introduced a workflow-based RFID tag witnessing and real-time information entry platform for addressing these challenges. To assess its potential in reducing mix-ups, we conducted a simulation experiment in semen preparation to analyze its error correction rate. Additionally, we evaluated its impact on work efficiency, specifically in operation and data entry. Furthermore, we compared the cycle costs between paper labels and RFID tags. Finally, we retrospectively analyzed clinical outcomes of 20,424 oocyte retrieval cycles and 15,785 frozen embryo transfer cycles, which were divided into paper label and RFID tag groups. RESULTS: The study revealed that comparing to paper labels, RFID tag witnessing corrected 100% of tag errors, didn't affect gamete/embryo operations, and notably shorten the time of entering data, but the cycle cost of RFID tags was significantly higher. However, no significant differences were observed in fertilization, embryo quality, blastocyst rates, clinical pregnancy, and live birth rates between two groups. CONCLUSIONS: RFID tag witnessing doesn't negatively impact gamete/embryo operation, embryo quality and pregnancy outcomes, but it potentially reduces the risk of mix-ups or errors. Despite highly increased cost, integrating RFID tag witnessing with real-time information entry can remarkably decrease the data entry time, substantially improving the work efficiency. This workflow-based management platform also enhances operational safety, ensures medical informational integrity, and boosts embryologist's confidence.

FASLG as a Key Member of Necroptosis Participats in Acute Myocardial Infarction by Regulating Immune Infiltration.

Background: Acute myocardial infarction (AMI) is a major cause of human health risk. Necroptosis is a newly and recently reported mode of cell death, whose role in AMI has not been fully elucidated. This study aimed to search for necroptosis biomarkers associated with the occurrence of AMI and to explore their possible molecular mechanisms through bioinformatics analysis. Methods: The dataset GSE48060 was used to perform weighted gene co-expression network analysis (WGCNA) and differential analysis. Key modules, differential genes, and necroptosis-related genes (NRGs) were intersected to obtain candidate biomarkers. Groups were classified and differentially analyzed according to the expression of the key biomarker. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, gene set enrichment analysis (GSEA), and construction of protein-protein interaction (PPI) networks are performed on differentially expressed genes (DEGs). Finally, CIBERSORT was used to assess immune cell infiltration in AMI and the correlation of key biomarkers with immune cells. Immune cell infiltration analysis revealed the correlation between FASLG and multiple screened immune cells. Results: WGCNA determined that the MEsaddlebrown module was the most significantly associated with AMI. Intersecting it with DEGs as well as NRGs, we obtained two key genes, FASLG and IFNG. But only FASLG showed statistically significant differences between the AMI group and the normal control group. Further analysis suggested that the down-regulation of FASLG may exert its function through the regulation of the central genes CD247 and YES1. Furthermore, FASLG was positively correlated with T-cell CD4 memory activation and T-cell gamma delta, and negatively correlated with macrophage M0. Conclusion: In conclusion, FASLG and its regulatory genes CD247 and YES1 might be involved in the development of AMI by regulating immune cell infiltration. FASLG might be a potential biomarker for AMI and provides a new direction for the diagnosis of AMI.

Capsaicin exerts synergistic pro-apoptotic effects with cisplatin in TSCC through the calpain pathway via TRPV1.

Capsaicin (CAP) exerts significant anti-tumor effects on a variety of tumors, with low intrinsic toxicity. Cisplatin (DDP) is currently the first-line drug for the treatment of oral cancer; however, its clinical efficacy is impeded by chemoresistance and negligible side effects. Whether the combined use of CAP and DDP has a synergistic antitumor effect on tongue squamous cell carcinoma (TSCC) cells and its underlying mechanisms remains unclear. The present study revealed that CAP reduced the activity of TSCC cells in a dose- and time-dependent manner. We also observed changes in the mitochondrial functional structure of TSCC cells, along with the induction of mitochondrial apoptosis. Moreover, when CAP was combined with DDP, a synergistic cytotoxic effect on TSCC cells was observed, which had a significant impact on inducing apoptosis, inhibiting proliferation, and disrupting the mitochondrial membrane potential in TSCC cells compared to the single-drug treatment and control groups. These effects are associated with TRPV1, a high-affinity CAP receptor. The combined use of CAP and DDP can activate the TRPV1 receptor, resulting in intracellular Ca2+ overload and activation of the calpain pathway, ultimately leading to mitochondrial apoptosis. This potential mechanism was validated in TSCC xenograft models. In conclusion, our findings clearly demonstrate that CAP exerts synergistic pro-apoptotic effects with DDP in TSCC through the calpain pathway mediated by TRPV1. Thus, CAP can be considered an effective adjuvant drug for DDP in the treatment of TSCC.

Retinal microvascular changes in patients with pancreatitis and their clinical significance.

Acute pancreatitis, a common exocrine inflammatory disease affecting the pancreas, is characterized by intense abdominal pain and multiple organ dysfunction. However, the alterations in retinal blood vessels among individuals with acute pancreatitis remain poorly understood. This study employed optical coherence tomography angiography (OCTA) to examine the superficial and deep retinal blood vessels in patients with pancreatitis. Sixteen patients diagnosed with pancreatitis (32 eyes) and 16 healthy controls (32 eyes) were recruited from the First Affiliated Hospital of Nanchang University for participation in the study. Various ophthalmic parameters, such as visual acuity, intraocular pressure, and OCTA image for retina consisting of the superficial retinal layer (SRL) and the deep retinal layer (DRL), were recorded for each eye. The study observed the superficial and deep retinal microvascular ring (MIR), macrovascular ring (MAR), and total microvessels (TMI) were observed. Changes in retinal vascular density in the macula through annular partitioning (C1-C6), hemispheric quadrant partitioning (SR, SL, IL, and IR), and early diabetic retinopathy treatment studies (ETDRS) partitioning methods (R, S, L, and I). Correlation analysis was employed to investigate the relationship between retinal capillary density and clinical indicators. Our study revealed that in the superficial retinal layer, the vascular density of TMI, MIR, MAR, SR, IR, S, C2, C3 regions were significantly decreased in patients group compared with the normal group. For the deep retinal layer, the vascular density of MIR, SR, S, C1, C2 regions also reduced in patient group. The ROC analysis demonstrated that OCTA possesses significant diagnostic performance for pancreatitis. In conclusion, patients with pancreatitis may have retinal microvascular dysfunction, and OCTA can be a valuable tool for detecting alterations in ocular microcirculation in pancreatitis patients in clinical practice.

Reduced syncytin-1 regulates trophoblast invasion and apoptosis in preeclampsia.

INTRODUCTION: Preeclampsia is a pregnancy-specific disorder characterized by de novo development of hypertension and proteinuria over 20 weeks gestation that has been associated with the dysfunction of trophoblasts. Current evidence suggests that syncytin-1 plays an important role in the non-fusogenic biological activity of trophoblasts, except for specific fusogenic function. However, the underlying mechanism remains unclear. METHODS: The expression and location of syncytin-1 in normal and the late-onset preeclampsia placentas were detected by quantitative real-time PCR, western blotting and immunofluorescence. Morphological and apoptosis analysis were processed in placentas. The ex vivo extravillous explant culture model was used to explore the effect of syncytin-1 on EVT outgrowths. Real-time quantitative PCR and immunoblotting were used to calculate syncytin-1 levels in the trophoblast cells before and after syncytin-1 knockdown or overexpression. CCK-8 assay was used to detect the cell viability. TUNEL staining and immunoblotting were processed in trophoblast cells. Transwell assays and wound healing assays were utilize to assess the invasion and migration of trophoblastic cells. Conditional knockout of syncytin-a mouse model was conducted to present the change of placentas in vivo. The ex vivo extravillous explant culture model was used to explore the effect of syncytin-1 on EVT outgrowths. Western blotting was used to identify the key proteins of PI3K/Akt pathways and invasion-related proteins in trophoblast cells. RESULTS AND DISCUSSION: Here, reduced syncytin-1 was identified in the late-onset preeclampsia placentas. Reduced syncytin-1 may attenuates the EMT process by promoting apoptosis, inhibiting proliferation and invasion by suppressed PI3K/Akt pathway in trophoblast cells. Our findings provide novel insights into the non-fusogenic biological function of reduced syncytin-1 that may be involves in the pathogenesis of preeclampsia.

Correction: Liu et al. Tamarixia radiata Behaviour Is Influenced by Volatiles from Both Plants and Diaphorina citri Nymphs. Insects 2019, 10, 141.

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CRISPR Screening and Comparative LC-MS Analysis Identify Genes Mediating Efficacy of Delamanid and Pretomanid against Mycobacterium tuberculosis.

Tuberculosis (TB), the leading cause of death from bacterial infections worldwide, results from infection with Mycobacterium tuberculosis (Mtb). The antitubercular agents delamanid (DLM) and pretomanid (PMD) are nitroimidazole prodrugs that require activation by an enzyme intrinsic to Mtb; however, the mechanism(s) of action and the associated metabolic pathways are largely unclear. Profiling of the chemical-genetic interactions of PMD and DLM in Mtb using combined CRISPR screening reveals that the mutation of rv2073c increases susceptibility of Mtb to these nitroimidazole drugs both in vitro and in infected mice, whereas mutation of rv0078 increases drug resistance. Further assays show that Rv2073c might confer intrinsic resistance to DLM/PMD by interfering with inhibition of the drug target, decaprenylphophoryl-2-keto-b-D-erythro-pentose reductase (DprE2), by active nicotinamide adenine dinucleotide (NAD) adducts. Characterization of the metabolic pathways of DLM/PMD in Mtb using a combination of chemical genetics and comparative liquid chromatography-mass spectrometry (LC-MS) analysis of DLM/PMD metabolites reveals that Rv0077c, which is negatively regulated by Rv0078, mediates drug resistance by metabolizing activated DLM/PMD. These results might guide development of new nitroimidazole prodrugs and new regimens for TB treatment.