A tissue-like neurotransmitter sensor for the brain and gut.

Neurotransmitters play essential roles in regulating neural circuit dynamics both in the central nervous system as well as at the peripheral, including the gastrointestinal tract1-3. Their real-time monitoring will offer critical information for understanding neural function and diagnosing disease1-3. However, bioelectronic tools to monitor the dynamics of neurotransmitters in vivo, especially in the enteric nervous systems, are underdeveloped. This is mainly owing to the limited availability of biosensing tools that are capable of examining soft, complex and actively moving organs. Here we introduce a tissue-mimicking, stretchable, neurochemical biological interface termed NeuroString, which is prepared by laser patterning of a metal-complexed polyimide into an interconnected graphene/nanoparticle network embedded in an elastomer. NeuroString sensors allow chronic in vivo real-time, multichannel and multiplexed monoamine sensing in the brain of behaving mouse, as well as measuring serotonin dynamics in the gut without undesired stimulations and perturbing peristaltic movements. The described elastic and conformable biosensing interface has broad potential for studying the impact of neurotransmitters on gut microbes, brain-gut communication and may ultimately be extended to biomolecular sensing in other soft organs across the body.

Reconstruction of dynamic mammary mini gland in vitro for normal physiology and oncogenesis.

Organoid culture has been extensively exploited for normal tissue reconstruction and disease modeling. However, it is still challenging to establish organoids that mimic in vivo-like architecture, size and function under homeostatic conditions. Here we describe the development of a long-term adult stem cell-derived mammary mini gland culture system that supports robust three-dimensional outgrowths recapitulating the morphology, scale, cellular context and transcriptional heterogeneity of the normal mammary gland. The self-organization ability of stem cells and the stability of the outgrowths were determined by a coordinated combination of extracellular matrix, environmental signals and dynamic physiological cycles. We show that these mini glands were hormone responsive and could recapitulate the entire postnatal mammary development including puberty, estrus cycle, lactation and involution. We also observed that these mini glands maintained the presence of mammary stem cells and could also recapitulate the fate transition from embryonic bipotency to postnatal unipotency in lineage tracing assays. In addition, upon induction of oncogene expression in the mini glands, we observed tumor initiation in vitro and in vivo in a mouse model. Together, this study provides an experimental system that can support a dynamic miniature mammary gland for the study of physiologically relevant, complex biological processes.

NME4 mediates metabolic reprogramming and promotes nonalcoholic fatty liver disease progression.

Nonalcoholic fatty liver disease (NAFLD) is mainly characterized by excessive fat accumulation in the liver, and it is associated with liver-related complications and adverse systemic diseases. NAFLD has become the most prevalent liver disease; however, effective therapeutic agents for NAFLD are still lacking. We combined clinical data with proteomics and metabolomics data, and found that the mitochondrial nucleoside diphosphate kinase NME4 plays a central role in mitochondrial lipid metabolism. Nme4 is markedly upregulated in mice fed with high-fat diet, and its expression is positively correlated with the level of steatosis. Hepatic deletion of Nme4 suppresses the progression of hepatic steatosis. Further studies demonstrated that NME4 interacts with several key enzymes in coenzyme A (CoA) metabolism and increases the level of acetyl-CoA and malonyl-CoA, which are the major lipid components of the liver in NAFLD. Increased level of acetyl-CoA and malonyl-CoA  lead to increased triglyceride levels and lipid accumulation in the liver. Taken together, these findings reveal that NME4 is a critical regulator of NAFLD progression and a potential therapeutic target for NAFLD.

Autophagy dysfunction contributes to NLRP1 inflammasome-linked depressive-like behaviors in mice.

BACKGROUND: Major depressive disorder (MDD) is a common but severe psychiatric illness characterized by depressive mood and diminished interest. Both nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 1 (NLRP1) inflammasome and autophagy have been reported to implicate in the pathological processes of depression. However, the mechanistic interplay between NLRP1 inflammasome, autophagy, and depression is still poorly known. METHODS: Animal model of depression was established by chronic social defeat stress (CSDS). Depressive-like behaviors were determined by social interaction test (SIT), sucrose preference test (SPT), open field test (OFT), forced swim test (FST), and tail-suspension test (TST). The protein expression levels of NLRP1 inflammasome complexes, pro-inflammatory cytokines, phosphorylated-phosphatidylinositol 3-kinase (p-PI3K)/PI3K, phosphorylated-AKT (p-AKT)/AKT, phosphorylated-mechanistic target of rapamycin (p-mTOR)/mTOR, brain-derived neurotrophic factor (BDNF), phosphorylated-tyrosine kinase receptor B (p-TrkB)/TrkB, Bcl-2-associated X protein (Bax)/B-cell lymphoma-2 (Bcl2) and cleaved cysteinyl aspartate-specific proteinase-3 (caspase-3) were examined by western blotting. The mRNA expression levels of pro-inflammatory cytokines were tested by quantitative real-time PCR. The interaction between proteins was detected by immunofluorescence and coimmunoprecipitation. Neuronal injury was assessed by Nissl staining. The autophagosomes were visualized by transmission electron microscopy. Nlrp1a knockdown was performed using an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion. RESULTS: CSDS exposure caused a bidirectional change in hippocampal autophagy function, which was activated in the initial period but impaired at the later stage. In addition, CSDS exposure increased the expression levels of hippocampal NLRP1 inflammasome complexes, pro-inflammatory cytokines, p-PI3K, p-AKT and p-mTOR in a time-dependent manner. Interestingly, NLRP1 is immunoprecipitated with mTOR but not PI3K/AKT and CSDS exposure facilitated the immunoprecipitation between them. Hippocampal Nlrp1a knockdown inhibited the activity of PI3K/AKT/mTOR signaling, rescued the impaired autophagy and ameliorated depressive-like behavior induced by CSDS. In addition, rapamycin, an autophagy inducer, abolished NLRP1 inflammasome-driven inflammatory reactions, alleviated depressive-like behavior and exerted a neuroprotective effect. CONCLUSIONS: Autophagy dysfunction contributes to NLRP1 inflammasome-linked depressive-like behavior in mice and the regulation of autophagy could be a valuable therapeutic strategy for the management of depression.

Evaluation of clinical characteristics and risk factors associated with Chlamydia psittaci infection based on metagenomic next-generation sequencing.

INTRODUCTION: Psittacosis is a zoonosis caused by Chlamydia psittaci, the clinical manifestations of Psittacosis range from mild illness to fulminant severe pneumonia with multiple organ failure. This study aimed to evaluate the clinical characteristics of Chlamydia psittaci infection diagnosed based on metagenomic next-generation sequencing(mNGS), as well as the risk factors affecting the progress of Chlamydia psittaci infection, in order to improve the effect of therapeutics. METHODS: We retrospectively analyzed the clinical data of patients infected with chlamydia psittaci in the First Affiliated Hospital of Nanchang University from January 2021 to December 2021. The patient's past medical history, clinical manifestations, laboratory examinations, chest CT results, treatment status, and prognosis data were collected. we also investigated both the pathogenic profile characteristics and the lower respiratory tract microbiota of patients with Chlamydia psittaci pneumonia using mNGS. RESULTS: All cases of Chlamydia psittaci in our research have been confirmed by mNGS. Among 46 cases of Chlamydia psittaci pneumonia, Poultry exposure was reported in 35 cases. In severe cases of Chlamydia psittaci pneumonia, Neutrophils, Procalcitonin (PCT), Lactate Dehydrogenase (LDH), Hydroxybutyrate Dehydrogenase (HBDH), Creatine Kinase Isoenzymes-B (CK-MB) and D-Dimer levels were remarkably higher than that of non-severe cases, except for lymphocytes (all P < 0.05). Chest CT scans showed Bilateral (77.8%), multiple lobar lungs (85.2%), pleural effusions (44.4%) involvement in those suffering from severe Chlamydia psittaci pneumonia, whereas its incidence was 0%, 21.1% and 10.5% in non-severe patients, respectively (P < 0.05). Multivariate analysis revealed that higher lymphocyte concentrations (OR 0.836, 95% CI 0.714-0.962, P = 0.041) were the only protective factor for survival. mNGS results indicated that 41.3% of patients (19/46) had suspected coinfections with a coinfection rate of 84.2% (16/19) in the severe group, much higher than that in the non severe group (p < 0.05). No significantly different profiles of lower respiratory tract microbiota diversity were found between non severe group and severe group. CONCLUSION: A history of poultry exposure in patients can serve as an important basis for diagnosing Chlamydia psittaci pneumonia, and patients with severe Chlamydia psittaci pneumonia are more likely to develop elevated inflammatory biomarkers as well as elevated cardiac markers. Higher lymphocyte concentrations are protective factors associated with severe C. psittaci pneumonia. The higher proportion of patients with coinfections in our study supports the use of mNGS for comprehensive early detection of respiratory infections in patients with C. psittaci pneumonia.

Kinase regulators evolved into two families by gain and loss of ability to bind plant steroid receptors.

All biological functions evolve by fixing beneficial mutations and removing deleterious ones. Therefore, continuously fixing and removing the same essential function to separately diverge monophyletic gene families sounds improbable. Yet, here we report that brassinosteroid insensitive1 kinase inhibitor1 (BKI1)/membrane-associated kinase regulators (MAKRs) regulating a diverse function evolved into BKI1 and MAKR families from a common ancestor by respectively enhancing and losing ability to bind brassinosteroid receptor brassinosteroid insensitive1 (BRI1). The BKI1 family includes BKI1, MAKR1/BKI1-like (BKL) 1, and BKL2, while the MAKR family contains MAKR2-6. Seedless plants contain only BKL2. In seed plants, MAKR1/BKL1 and MAKR3, duplicates of BKL2, gained and lost the ability to bind BRI1, respectively. In angiosperms, BKL2 lost the ability to bind BRI1 to generate MAKR2, while BKI1 and MAKR6 were duplicates of MAKR1/BKL1 and MAKR3, respectively. In dicots, MAKR4 and MAKR5 were duplicates of MAKR3 and MAKR2, respectively. Importantly, BKI1 localized in the plasma membrane, but BKL2 localized to the nuclei while MAKR1/BKL1 localized throughout the whole cell. Importantly, BKI1 strongly and MAKR1/BKL1 weakly inhibited plant growth, but BKL2 and the MAKR family did not inhibit plant growth. Functional study of the chimeras of their N- and C-termini showed that only the BKI1 family was partially reconstructable, supporting stepwise evolution by a seesaw mechanism between their C- and N-termini to alternately gain an ability to bind and inhibit BRI1, respectively. Nevertheless, the C-terminal BRI1-interacting motif best defines the divergence of BKI1/MAKRs. Therefore, BKI1 and MAKR families evolved by gradually gaining and losing the same function, respectively, extremizing divergent evolution and adding insights into gene (BKI1/MAKR) duplication and divergence.

In-depth comparative pathogenome, virulome, and resistome analysis of an extensive drug resistant Ralstonia mannitolilytica strain isolated from blood.

INTRODUCTION: Ralstonia mannitolilytica is an global opportunistic pathogen responsible for various diseases. In this study, we reported the genome of a R. mannitolilytica isolate responsible for bacteremia in an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: Bacterial identification was performed with a Vitek2™ Automated System and 16S rRNA sequencing with BLASTn against the Non-Redundant Protein Sequence (Nr) database. Genome sequencing and analysis were performed using PacBio RS II sequencer, Hierarchical Genome Assembly Process assembly, as well as multiple annotation databases to better understand the innate features. Antibiotic resistance genes and virulence factors were specifically identified through Antibiotic Resistance Genes database and Virulence Factors of Pathogenic Bacteria databases. RESULTS: The complete genome sequence was assembled into two chromosomes with 3,495,817 bp and 1,342,871 bp in length and GC% of 65.37 % and 66.43 %, respectively. The two chromosomes were fully annotated. In chromosome 1 and 2, 19 and 14 antibiotic resistant genes and 48 and 55 virulence factors were predicted, respectively. Specifically, beta-lactam resistance genes blaOXA-443, blaOXA-444 were acquired. CONCLUSIONS: This study aids in the understanding of the innate features of R. mannitolilytica in AECOPD.

The mutation of Japanese encephalitis virus envelope protein residue 389 attenuates viral neuroinvasiveness.

The envelope (E) protein of the Japanese encephalitis virus (JEV) is a key protein for virus infection and adsorption of host cells, which determines the virulence of the virus and regulates the intensity of inflammatory response. The mutation of multiple aa residues in the E protein plays a critical role in the attenuated strain of JEV. This study demonstrated that the Asp to Gly, Ser, and His mutation of the E389 site, respectively, the replication ability of the viruses in cells was significantly reduced, and the viral neuroinvasiveness was attenuated to different degrees. Among them, the mutation at E389 site enhanced the E protein flexibility contributed to the attenuation of neuroinvasiveness. In contrast, less flexibility of E protein enhanced the neuroinvasiveness of the strain. Our results indicate that the mechanism of attenuation of E389 aa mutation attenuates neuroinvasiveness is related to increased flexibility of the E protein. In addition, the increased flexibility of E protein enhanced the viral sensitivity to heparin inhibition in vitro, which may lead to a decrease in the viral load entering brain. These results suggest that E389 residue is a potential site affecting JEV virulence, and the flexibility of the E protein of aa at this site plays an important role in the determination of neuroinvasiveness.

Diclofenac sodium effectively inhibits the biofilm formation of Staphylococcus epidermidis.

Staphylococcus epidermidis is an opportunistic pathogen commonly implicated in medical device-related infections. Its propensity to form biofilms not only leads to chronic infections but also exacerbates the issue of antibiotic resistance, necessitating high-dose antimicrobial treatments. In this study, we explored the use of diclofenac sodium, a non-steroidal anti-inflammatory drug, as an anti-biofilm agent against S. epidermidis. In this study, crystal violet staining and confocal laser scanning microscope analysis showed that diclofenac sodium, at subinhibitory concentration (0.4 mM), significantly inhibited biofilm formation in both methicillin-susceptible and methicillin-resistant S. epidermidis isolates. MTT assays demonstrated that 0.4 mM diclofenac sodium reduced the metabolic activity of biofilms by 25.21-49.01% compared to untreated controls. Additionally, the treatment of diclofenac sodium resulted in a significant decrease (56.01-65.67%) in initial bacterial adhesion, a crucial early phase of biofilm development. Notably, diclofenac sodium decreased the production of polysaccharide intercellular adhesin (PIA), a key component of the S. epidermidis biofilm matrix, in a dose-dependent manner. Real-time quantitative PCR analysis revealed that diclofenac sodium treatment downregulated biofilm-associated genes icaA, fnbA, and sigB and upregulated negative regulatory genes icaR and luxS, providing potential mechanistic insights. These findings indicate that diclofenac sodium inhibits S. epidermidis biofilm formation by affecting initial bacterial adhesion and the PIA synthesis. This underscores the potential of diclofenac sodium as a supplementary antimicrobial agent in combating staphylococcal biofilm-associated infections.

The role of male hormones in bacterial infections: enhancing Staphylococcus aureus virulence through testosterone-induced Agr activation.

Staphylococcus aureus is a notorious pathogen predominantly involved in skin and soft tissue infections, exhibiting a distinct innate sex bias. This study explores the influence of testosterone on the virulence of S. aureus and elucidates its underlying mechanisms. Utilizing a skin abscess model in intact and castrated male mice, we assessed the effects of testosterone on S. aureus pathogenicity. Compared to controls, castrated mice showed significantly reduced abscess sizes and decreased bacterial loads, highlighting the role of testosterone in modulating the severity of S. aureus infections. In vitro experiments revealed that testosterone enhances the hemolytic activity, cytotoxicity, and oxidative stress resistance of S. aureus. Real-time quantitative PCR analysis showed a significant upregulation of the genes encoding α-hemolysin (hla) and phenol-soluble modulin (psmα). Importantly, testosterone treatment significantly enhanced the expression of the accessory gene regulator (Agr) quorum-sensing system components (agrC, agrA, agrB, agrD), while the SaeRS system (saeR, saeS, and sbi) exhibited only slight changes. Gene knockout experiments revealed that deletion of agrC, rather than saeRS and agrBD, abolishes the testosterone-induced enhancement of hemolysis and gene expression, underscoring the key role of AgrC. Molecular docking simulations indicated a direct interaction between testosterone and AgrC protein, with a strong binding affinity at the active site residue SER201. This study provides new insights into the mechanistic basis of how testosterone enhances the pathogenicity of S. aureus, potentially contributing to increased male susceptibility to S. aureus infections and offering a targeted approach for therapeutic interventions.

Nucleotide at position 66 of NS2A in Japanese encephalitis virus is associated with the virulence and proliferation of virus.

Most wild strains of Japanese encephalitis virus (JEV) produce NS1' protein, which plays an important role in viral infection and immune escape. The G66A nucleotide mutation in NS2A gene of the wild strain SA14 prevented the ribosomal frameshift that prevented the production of NS1' protein, thus reduced the virulence. In this study, the 66th nucleotide of the NS2A gene of SA14 was mutated into A, U or C, respectively. Both the G66U and G66C mutations cause the E22D mutation of the NS2A protein. Subsequently, the expression of NS1' protein, plaque size, replication ability, and virulence to mice of the three mutant strains were examined. The results showed that the three mutant viruses could not express NS1' protein, and their proliferation ability in nerve cells and virulence to mice were significantly reduced. In addition, the SA14(G66C) was less virulent than the other two mutated viruses. Our results indicate that only when G is the 66th nucleotide of NS2A, the JEV can produce NS1' protein, which affects the virulence.

Identification of drug-side effect association via correntropy-loss based matrix factorization with neural tangent kernel.

Adverse drug reactions include side effects, allergic reactions, and secondary infections. Severe adverse reactions can cause cancer, deformity, or mutation. The monitoring of drug side effects is an important support for post marketing safety supervision of drugs, and an important basis for revising drug instructions. Its purpose is to timely detect and control drug safety risks. Traditional methods are time-consuming. To accelerate the discovery of side effects, we propose a machine learning based method, called correntropy-loss based matrix factorization with neural tangent kernel (CLMF-NTK), to solve the prediction of drug side effects. Our method and other computational methods are tested on three benchmark datasets, and the results show that our method achieves the best predictive performance.

A risk prediction model for delayed bleeding after ESD for gastric precancerous lesions.

OBJECTIVE: To investigate the risk factors for delayed postoperative bleeding after endoscopic submucosal dissection (ESD) in patients with gastric precancerous lesions and to construct a risk prediction model. METHODS: This retrospective analysis included clinical data from patients with gastric precancerous lesions who underwent ESD at Wuhan University People's Hospital between November 2016 and June 2022. An XGBoost model was built to predict delayed bleeding after ESD using risk factors identified by univariable and multivariate logistic regression analysis. The model was evaluated using receiver operating characteristic curves (ROC), and SHapely Additive exPlanations (SHAP) analysis was used to interpret the model. RESULTS: Seven factors were statistically associated with delayed postoperative bleeding in gastric precancerous lesions after ESD: age, low-grade intraepithelial neoplasia, hypertension, lesion size ≥ 40 mm, operative time ≥ 120 min, female, and nonuse of hemoclips. A risk prediction model was established. In the training cohort, the model achieved an AUC of 0.97 (0.96-0.98), a sensitivity of 0.90, a specificity of 0.94, and an F1 score of 0.91. In the validation cohort, the AUC was 0.94(0.90-0.98), with a sensitivity of 0.85, a specificity of 0.89, and an F1 score of 0.85. In the test cohort, the AUC was 0.94 (0.89-0.99), the sensitivity was 0.80, the specificity was 0.92, and the F1 score was 0.84, indicating strong predictive capability. CONCLUSION: In this study, an XGBoost prediction model for assessing the risk of delayed postoperative bleeding after ESD in patients with gastric precancerous lesions was developed and validated. This model can be applied in clinical practice to effectively predict the risk of post-ESD bleeding for individual patients.

Evaluation of deep learning-based reconstruction late gadolinium enhancement images for identifying patients with clinically unrecognized myocardial infarction.

BACKGROUND: The presence of infarction in patients with unrecognized myocardial infarction (UMI) is a critical feature in predicting adverse cardiac events. This study aimed to compare the detection rate of UMI using conventional and deep learning reconstruction (DLR)-based late gadolinium enhancement (LGEO and LGEDL, respectively) and evaluate optimal quantification parameters to enhance diagnosis and management of suspected patients with UMI. METHODS: This prospective study included 98 patients (68 men; mean age: 55.8 ± 8.1 years) with suspected UMI treated at our hospital from April 2022 to August 2023. LGEO and LGEDL images were obtained using conventional and commercially available inline DLR algorithms. The myocardial signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and percentage of enhanced area (Parea) employing the signal threshold versus reference mean (STRM) approach, which correlates the signal intensity (SI) within areas of interest with the average SI of normal regions, were analyzed. Analysis was performed using the standard deviation (SD) threshold approach (2SD-5SD) and full width at half maximum (FWHM) method. The diagnostic efficacies based on LGEDL and LGEO images were calculated. RESULTS: The SNRDL and CNRDL were two times better than the SNRO and CNRO, respectively (P < 0.05). Parea-DL was elevated compared to Parea-O using the threshold methods (P < 0.05); however, no intergroup difference was found based on the FWHM method (P > 0.05). The Parea-DL and Parea-O also differed except between the 2SD and 3SD and the 4SD/5SD and FWHM methods (P < 0.05). The receiver operating characteristic curve analysis revealed that each SD method exhibited good diagnostic efficacy for detecting UMI, with the Parea-DL having the best diagnostic efficacy based on the 5SD method (P < 0.05). Overall, the LGEDL images had better image quality. Strong diagnostic efficacy for UMI identification was achieved when the STRM was ≥ 4SD and ≥ 3SD for the LGEDL and LGEO, respectively. CONCLUSIONS: STRM selection for LGEDL magnetic resonance images helps improve clinical decision-making in patients with UMI. This study underscored the importance of STRM selection for analyzing LGEDL images to enhance diagnostic accuracy and clinical decision-making for patients with UMI, further providing better cardiovascular care.

Sleeve gastrectomy improves cardiac function and glucose-lipid metabolism disorder in obese rats induced by a high-fat and high-sugar diet.

Obesity is affecting global health with multiple complications, including cardiac dysfunction. Currently, it is uncertain whether drug therapy should be applied in the early stages of obesity-induced cardiac dysfunction, with weight reduction as the first choice. Sleeve gastrectomy (SG) has been widely used to treat obesity and its complications, showing promising results. However, it remains unclear whether SG can alleviate obesity-induced cardiac dysfunction. A sudden decline in body weight and food intake was observed in both the obese and obese + SG groups, with a higher rate of increase observed in the Obese group. Elevated levels of plasma glucose, serum insulin, and glycated haemoglobin in obese rats were significantly reduced by SG. Markedly increased levels of alanine transaminase, aspartate transaminase, alkaline phosphatase albumin, total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels, elevated values of heart rate, left ventricular end-systolic pressure, left ventricular end-diastolic pressure, systolic pressure, and end diastolic pressure, and decreased value of stroke volume were observed in obese rats, which were sharply reversed by SG. Furthermore, enhanced pathological changes, including inflammatory cell infiltration and loss of cytoplasm striations, enhanced oil red O staining, increased TUNEL-positive cells, upregulated Bax and cleaved-caspase-3, and downregulated Bcl-2, were observed in obese rats, which were notably alleviated by SG. Lastly, the increased levels of relative proteins observed in obese rats were significantly reduced by SG. In conclusion, SG improved cardiac function and glucose-lipid metabolism disorders in obese rats induced by a high-fat and high-sugar diet.

A Reinterpretation of Paracolpium in Radical Hysterectomy: New Insights into Its Surgical Implication.

OBJECTIVE: To reinterpret the surgical anatomy of paracolpium in radical hysterectomy and to explore its implications for the surgery. SETTING: The term "paracolpium" first defined by Fothergill in 1907, is essential in radical hysterectomy. However, several challenges remain unresolved. These include: (1) inconsistent terminology in relation to its defined attributes; (2) the lack of consensus on anatomical landmarks; (3) unclear associations with the cardinal and sacral ligaments; and (4) the critical implications and requirements of paracolpium resection in radical hysterectomy practices. PARTICIPANTS: A patient in her 60s diagnosed with stage IB2 cervical cancer was enrolled in a clinical trial and assigned to the laparoscopic surgery group. A step-by-step, narrated video demonstration. INTERVENTIONS: During the procedure, post-excision of the uterosacral, cardinal, and vesicovaginal ligaments, we identified a ligament-like structure situated between the middle third of the vagina and the pelvic wall. We have termed this structure the "paracolpium ligament." A detailed anatomical description was performed, outlining its crucial attachments: • Medial attachment: middle third of the vagina • Lateral attachment: tendinous arch of the pelvic fascia (TAPF) • Cranial attachment: cardinal-uterosacral ligaments confluence • Caudal attachment: pubococcygeus muscle fascia • Dorsal: paravaginal space • Ventral: pararectal space To ensure a safe dissection, the paracolpium ligament was exposed by removing anterior and posterior fat tissue. The extent of surgical resection was adapted based on the tumor's location. Extensive resection of the paracolpium ligament was essential when the tumor was localized to one side of the vagina to ensure complete removal of the disease; otherwise, preservation of the ligament was considered feasible. CONCLUSION: In this video, we meticulously name and define the "paracolpium ligament," providing groundbreaking insights into its anatomical and surgical implications in radical hysterectomy. Our findings contribute to a better understanding of surgical anatomy for cervical cancer.

Peak enhancement in contrast-enhanced ultrasound for assessing endoscopic disease activity in patients with Crohn's disease: a meta-analysis.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) has been proposed as a valuable tool for detecting disease activity in patients with Crohn's disease (CD). However, previous studies have utilized different parameters, leading to variation in clinical assessment of this technique. PURPOSE: To assess the effectiveness of peak enhancement (PE) in CEUS for evaluating endoscopic disease activity in patients with CD. MATERIAL AND METHODS: Articles were obtained by searching PubMed, Embase, Web of Science, Wanfang, and CNKI databases. Only studies that investigated the effectiveness of PE in CEUS to discriminate endoscopic disease activity in patients with CD were considered. Pooled sensitivity and specificity were then calculated using a random effects model. RESULTS: Overall, seven studies were included. The endoscopic disease activity of CD was determined based on the simple endoscopic score for Crohn's disease and Crohn's Disease Endoscopic Index of Severity scores. Pooled results showed that a high PE was associated with increased detection efficacy for endoscopic disease activity in CD. Pooled sensitivity, specificity, and positive and negative likelihood ratios were 0.88 (95% confidence interval [CI] = 0.71-0.96), 0.88 (95% CI = 0.81-0.93), 7.60 (95% CI = 4.61-12.53), and 0.14 (95% CI = 0.05-0.35), respectively. The pooled receiver operating characteristic was 0.90 (95% CI = 0.87-0.92), suggesting a good discriminating efficacy of PE in CEUS for endoscopic disease activity of patients with CD. CONCLUSIONS: A high PE in CEUS displayed substantial distinguishing accuracy for assessing endoscopic disease activity of patients with CD.

CD47-a novel prognostic predicator in epithelial ovarian cancer and correlations with clinicopathological and gene mutation features.

BACKGROUND: Epithelial ovarian cancer (EOC) is insensitive to immunotherapy due to its poor immunogenicity; thus, suitable biomarkers need to be identified for better prognostic stratification and individualized treatment. CD47 is a novel immunotherapy target; however, its impact on EOC prognosis is controversial and correlation with genetic features is unclear. The aim of this study was to investigate the prognostic significance of CD47 and its correlations with biological behaviors and genetic features of EOC. METHODS: Immunohistochemistry (IHC) and next-generation sequencing (NGS) were performed to examine expressions of CD47, PD-L1, and genomic mutations in the tissue samples of 75 EOC patients. Various clinicopathologic and genomic features were then evaluated to determine their correlation with CD47 expression. Kaplan-Meier analysis and Cox regression analysis were used to identify independent prognostic factors. Risk score modeling was then established, and the predictive capacity of this model was further confirmed by nomogram analysis. RESULTS: CD47 was mainly expressed in the tumor cell membrane and cytoplasm, and the rate of high CD47 expression was 63.7%. CD47 expression was associated with various clinicopathological factors, including FIGO stage, CA125 and HE4 value, presence of multidisciplinary surgeries, presence and volume of ascites, lymph-node metastasis, Ki-67 index and platinum-resistant, as well as genetic characteristics like BRCA mutation, HRD status, and TP53 mutation in EOC. Patients with high CD47 expression showed worse prognosis than the low-expression group. Cox regression analysis demonstrated that CA125, CD47, and BRCA mutation were independent factors for EOC prognosis. Patients were then categorized into high-risk and low-risk subgroups based on the risk score of the aforementioned independent factors, and the prognosis of the high-risk group was worse than those of the low-risk group. The nomogram showed adequate discrimination with a concordance index of 0.777 (95% CI, 0.732-0.822). The calibration curve showed good consistency. CONCLUSION: CD47 correlated with various malignant biology and genetic characteristics of EOC and may play pivotal and multifaceted roles in the tumor microenvironment of EOC Finally, we constructed a reliable prediction model centered on CD47 and integrated CA125 and BRCA to better guide high-risk population management.

Characterisation of a SapYZU11@ZnFe2O4 biosensor reveals its mechanism for the rapid and sensitive colourimetric detection of viable Staphylococcus aureus in food matrices.

Although bacteriophage-based biosensors hold promise for detecting Staphylococcus aureus in food products in a timely, simple, and sensitive manner, the associated targeting mechanism of the biosensors remains unclear. Herein, a colourimetric biosensor SapYZU11@ZnFe2O4, based on a broad-spectrum S. aureus lytic phage SapYZU11 and a ZnFe2O4 nanozyme, was constructed, and its capacity to detect viable S. aureus in food was evaluated. Characterisation of SapYZU11@ZnFe2O4 revealed its effective immobilisation, outstanding biological activity, and peroxidase-like capability. The peroxidase activity of SapYZU11@ZnFe2O4 significantly decreased after the addition of S. aureus, potentially due to blockage of the nanozyme active sites. Moreover, SapYZU11@ZnFe2O4 can detect S. aureus from various sources and S. aureus isolates that phage SapYZU11 could not lyse. This may be facilitated by the adsorption of the special receptor-binding proteins on the phage tail fibre and wall teichoic acid receptors of S. aureus. Besides, SapYZU11@ZnFe2O4 exhibited remarkable sensitivity and specificity when employing colourimetric techniques to rapidly determine viable S. aureus counts in food samples, with a detection limit of 0.87 × 102 CFU/mL. Thus, SapYZU11@ZnFe2O4 has broad application prospects for the detection of viable S. aureus cells on food substrates.