Development of a dual-component biosensor for rapid and sensitive detection of influenza H7 and H5 subtypes.

The outbreak of highly pathogenic influenza virus subtypes, such as H7 and H5, presents a significant global health challenge, necessitating the development of rapid and sensitive diagnostic methods. In this study, we have developed a novel dual-component biosensor assembly, each component of which incorporates an antibody fused with a nano-luciferase subunit. Our results demonstrate the effectiveness of this biosensor in enabling the rapid and sensitive detection of influenza H7 and other subtypes. Additionally, we successfully applied the biosensor in paper-based assay and lateral flow assay formats, expanding its versatility and potential for field-deployable applications. Notably, we achieved effective detection of the H7N9 virus using this biosensor. Furthermore, we designed and optimized a dedicated biosensor to the sensitive detection of the influenza H5 subtype. Collectively, our findings underscore the significant potential of this dual-component biosensor assembly as a valuable and versatile tool for accurate and timely diagnosis of influenza virus infections, promising to advance the field of influenza diagnostics and contribute to outbreak management and surveillance efforts.

Increase of PCSK9 expression in diabetes promotes VEGFR2 ubiquitination to inhibit endothelial function and skin wound healing.

Diabetic foot ulcers (DFUs) are a serious vascular disease. Currently, no effective methods are available for treating DFUs. Pro-protein convertase subtilisin/kexin type 9 (PCSK9) regulates lipid levels to promote atherosclerosis. However, the role of PCSK9 in DFUs remains unclear. In this study, we found that the expression of PCSK9 in endothelial cells (ECs) increased significantly under high glucose (HG) stimulation and in diabetic plasma and vessels. Specifically, PCSK9 promotes the E3 ubiquitin-protein ligase NEDD4 binding to vascular endothelial growth factor receptor 2 (VEGFR2), which led to the ubiquitination of VEGFR2, resulting in its degradation and downregulation in ECs. Furthermore, PCSK9 suppresses the expression and activation of AKT, endothelial nitric oxide synthase (eNOS), and ERK1/2, leading to decreased nitric oxide (NO) production and increased superoxide anion (O2._) generation, which impairs vascular endothelial function and angiogenesis. Importantly, using evolocumab to limit the increase in PCSK9 expression blocked the HG-induced inhibition of NO production and the increase in O2._ production, as well as inhibited the phosphorylation and expression of AKT, eNOS, and ERK1/2. Moreover, evolocumab improved vascular endothelial function and angiogenesis, and promoted wound healing in diabetes. Our findings suggest that targeting PCSK9 is a novel therapeutic approach for treating DFUs.

Predictive Role of Elevated Neutrophil-Lymphocyte Ratio for Bone Metastasis in Esophageal Cancer.

PURPOSE: Research on bone metastasis in esophageal cancer (EC) is relatively limited. Once bone metastasis occurs in patients, their prognosis is poor, and it severely affects their quality of life. Currently, there is a lack of convenient tumor markers for early identification of bone metastasis in EC. Our research aims to explore whether neutrophil-lymphocyte ratio (NLR) can predict bone metastasis in patients with EC. METHODS: Retrospective analysis of clinical indicators was performed on 604 patients with EC. They were divided into groups based on whether or not there was bone metastasis, and the patients' coagulation-related tests, blood routine, tumor markers and other indicators were collected. The receiver operating characteristic curve (ROC) were used to determine the predictive ability of parameters such as NLR for bone metastasis in EC, and univariate and multivariate logistic regression analyses were conducted to determine the impact of each indicator on bone metastasis. Using binary logistic regression to obtain the predictive probability of NLR combined with tumor markers. RESULTS: ROC curves analysis suggested that the area under the curve (AUC) of the NLR was 0.681, with a sensitivity of 79.2% and a specificity of 52.6%, which can be used as a predictive factor for bone metastasis in EC. Multivariate logistic regression analysis showed that high NLR (odds ratio [OR]: 2.608, 95% confidence interval [CI]: 1.395-4.874, P = 0.003) can function as an independent risk factor for bone metastasis in patients with EC. Additionally, high PT, high APTT, high FDP, high CEA, high CA724, low hemoglobin, and low platelet levels can also predict bone metastasis in EC. When NLR was combined with tumor markers, the area under the curve was 0.760 (95% CI: 0.713-0.807, P < 0.001), significantly enhancing the predictability of bone metastasis in EC. CONCLUSION: NLR, as a convenient, non-invasive, and cost-effective inflammatory indicator, could predict bone metastasis in EC. Combining NLR with tumor markers can significantly improve the diagnostic accuracy of bone metastasis in EC.

Emerging pathogens Aerococcus urinae and Aerococcus sanguinicola from a Canadian tertiary care hospital.

Background: Aerococcus urinae and Aerococcus sanguinicola are emerging pathogens linked with urinary tract infections. We present a case series of A. urinae and A. sanguinicola isolates characterizing the spectrum of clinical presentation, microbiological characteristics and antimicrobial sensitivities. Methods: Retrospective chart review was performed on patients who grew positive cultures for A. urinae and A. sanguinicola identified on MALDI-TOF in Saskatchewan from January to June 2023. Demographic and clinical variables, antimicrobial susceptibility and prescription were documented. Results: This cohort (n = 115) had a median age 82 years. A. urinae and A. sanguinicola infections spanned from urinary tract infection (n = 96) to urosepsis (n = 6). These infections were predominantly monomicrobial (73.9%) and were susceptible to ceftriaxone, penicillin G and vancomycin. Antimicrobials were seldom prescribed within the urinary tract infection cohort (31.2%). Conclusion: Untreated A. urinae and A. sanguinicola infections can precipitate into urosepsis. The reported antimicrobial susceptibility for these Aerococcus isolates should be utilized to provide appropriate antimicrobial coverage.

Aerococcus urinae and Aerococcus sanguinicola are bacteria that can cause urine infections. They are often overlooked and thought to be unable to cause serious blood infections, such as sepsis. We collected data on 87 cases of A. urinae and 28 cases of A. sanguinicola to show that these bacteria can cause urine and blood infections in elderly patients. We also looked at other studies and summarized that patients with serious blood infections from these bacteria often had a previous urine infection from these same bacteria. These bacteria can be resistant to a common antibiotic used to treat urine infections. It is important to test and report if these bacteria are resistant to this common antibiotic and doctors must be aware that they can cause serious blood infections if not treated with the correct antibiotics.

Pretreatment pulmonary tumor necrosis is a promising prognostic imaging biomarker for first-line anti-PD-1/PD-L1 therapy in advanced lung squamous cell carcinoma: a multi-institutional, propensity score-matching cohort analysis.

Background: Tumor necrosis (TN) is a common feature in lung squamous cell carcinoma (LSCC), which could provide useful predictive and prognostic information. Objectives: This study aimed to investigate the effect of pretreatment pulmonary TN (PTN) on the prognosis of first-line anti-programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) inhibitor in advanced LSCC. Design: We conducted a retrospective study to analyze the association between the presence of PTN and clinical outcomes in advanced LSCC patients treated with anti-PD-1/PD-L1 inhibitors. Methods: Data from 240 eligible patients were collected from 27 hospitals across China between 2016 and 2020. The presence of PTN was assessed using contrast-enhanced chest computed tomography (CT) imaging at baseline. We utilized the Cox proportional-hazards regression model to analyze the association between PTN and clinical outcomes. In addition, to account for potential confounding factors and ensure comparability between groups, we employed propensity score-matching (PSM) analysis. Results: In the overall patient cohort, the presence of PTN was 39.6%. The median follow-up duration was 20.3 months. The positive PTN group exhibited a notably inferior median progression-free survival (PFS; 6.5 months vs 8.6 months, p = 0.012) compared to the negative PTN group. Within the Cox proportional-hazards regression model, PTN emerged as an independent predictor of unfavorable PFS (hazard ratio (HR) = 1.354, 95% confidence interval (CI): 1.002-1.830, p = 0.049). After PSM, the median PFS for the positive PTN group (6.5 months vs 8.0 months, p = 0.027) remained worse than that of the negative PTN group. Multivariate analyses also further underscored that the presence of PTN independently posed a risk for shorter PFS (HR = 1.494, 95% CI: 1.056-2.112, p = 0.023). However, no statistically significant difference in overall survival was observed between the two groups. Conclusion: Our study suggests that the presence of PTN on baseline contrast-enhanced chest CT is a potential negative prognostic imaging biomarker for the outcome of anti-PD-1/PD-L1 inhibitor therapy in advanced LSCC. Further studies are warranted to validate these findings and explore the underlying mechanisms.

Predicting anti-PD-1/PD-L1 inhibitor treatment outcomes: pulmonary tumor necrosis in lung squamous cell carcinoma Our study focused on lung squamous cell carcinoma (LSCC) patients receiving first-line anti-PD-1/PD-L1 therapy. We explored the impact of a feature called pretreatment pulmonary tumor necrosis (PTN) on their prognosis. PTN was identified in 39.6% of patients using baseline chest CT scans. Results revealed that patients with PTN had a shorter time without disease progression (median PFS of 6.5 months compared to 8.6 months) and a higher risk of unfavorable outcomes. This suggests that PTN may serve as a negative prognostic imaging marker for anti-PD-1/PD-L1 therapy in advanced LSCC. Further research is needed to confirm and understand these findings better.

Factors influencing the continuity of evidence-based practice in perioperative airway management for elderly patients with fractures: A qualitative study.

BACKGROUND: More and more evidence-based practices are emerging, but researchers mostly focus on short-term effects, resulting in evidence-based practices not being applied in the clinic in the long term. In this study, we took the evidence-based practice of perioperative airway management in elderly fracture patients as an example and adopted a descriptive phenomenological approach to understand the influencing factors of its sustainability to provide a reference basis for promoting the continuity of evidence-based practice in the clinic. AIM: To explore factors influencing the persistence of evidence-based practice in perioperative airway management in elderly patients with fractures. METHODS: This study was qualitative research. Nine nurses who implemented evidence-based practice in the orthopedic ward of a tertiary comprehensive hospital in Shanghai from September 2023 to October 2023 were selected using purposive sampling as research subjects. Semi-structured interviews were conducted with them, and the data were analyzed using the Colaizzi phenomenological analysis method based on the three dimensions and ten factors of the NHS sustainability model. RESULTS: Three main themes and ten subthemes were identified: Process aspects (benefits to patients, benefits to nurses, lack of follow-up, complex processes); staff aspects (insufficient human resources, inadequate training and education, lack of leadership support); and organizational environment aspects (inadequate infrastructure, poor patient compliance, poor doctor cooperation). CONCLUSION: Human resources, training and education, leadership support, infrastructure, and patient-physician collaboration are important factors influencing the sustainability of evidence-based practice for perioperative airway management in older patients with fractures.

Clinical value of low-dose three-dimensional reconstruction by multi-slice spiral computed tomography and by traditional X-ray in the diagnosis of distal radius epiphyseal injury in children.

OBJECTIVE: To compare the clinical value of multi-slice spiral computed tomography (MSCT) low-dose three-dimensional reconstruction and traditional X-ray in the auxiliary diagnosis of distal radius epiphyseal injury in children. METHODS: A retrospective analysis was performed on 105 children with distal radius bone scale injury (classified by Salter-Harris classification) admitted from March 2020 to June 2022. All children underwent MSCT three-dimensional reconstruction examination and traditional X-ray examination. The detection rate of epiphyseal injury of the distal radius was compared, along with the resolution, sensitivity and specificity. The image clarity and display degree of bone structure were analyzed. The radiation dose-related indicators and the time required for diagnosis were compared. RESULTS: The detection rate and diagnostic accuracy of MSCT (100%, 92.38%) was significantly higher than that of X-ray (76.19%, 64.76%). In terms of radiation dose index, the volume dose index CTDI of MSCT ranged from 1-5 mGy while the X-ray group ranged from 5-10 mGy. The dose length product (DLP) value of the MSCT group was lower than in the X-ray group (20-100 mGy·cm vs. 50-150 mGy·cm). The diagnostic scan time for MSCT was shorter than that of conventional X-ray. The acceptance rate with MSCT was 99%, significantly higher than that with conventional X-ray (85%). CONCLUSIONS: Low-dose three-dimensional reconstruction of MSCT in the diagnosis of epiphyseal injury of distal radius in children shows significant advantages over traditional CT in the detection rate, diagnostic accuracy, postoperative reduction quality evaluation, and radiation dose.

Disruption of the interaction between caveolae and Piezo1 promotes pressure overload-induced cardiac remodeling.

Piezo1 channels are activated by mechanical stress and play a significant role in cardiac hypertrophy and fibrosis. However, the molecular mechanisms underlying Piezo1 activation on the cell membrane following pressure overload remain unclear. Caveolae are known to mitigate mechanical forces and regulate Piezo1 function. Therefore, this study aimed to investigate the interaction between caveolae and Piezo1 in the development of pressure overload-induced cardiac remodeling. We observed reduced colocalization between Piezo1 and Caveolin-3 in hypertrophic cardiomyocytes following abdominal aortic constriction and Angiotensin-II treatment, accompanied by increased Piezo1 function and expression. Furthermore, enhanced Piezo1 function was also noted upon caveolae disruption using methyl-beta-cyclodextrin (mßCD). Thus, our findings suggested that pressure overload led to Piezo1 translocation from caveolae, thereby augmenting its function and expression, which may contribute to cardiac remodeling.

The efficacy of postoperative radiotherapy in resected pâ ¢A-N2 EGFR mutant and wild-type lung adenocarcinoma.

The resected pⅢA-N2 non-small-cell lung cancer (NSCLC) patients who could benefit from postoperative radiotherapy (PORT) are not well-defined. The study explored the role of PORT on EGFR mutant and wild-type NSCLC patients. We retrospectively searched for resected pIIIA-N2 lung adenocarcinoma patients who underwent EGFR mutation testing. 80 patients with EGFR wild-type and 85 patients with EGFR mutation were included. 62 patients received PORT. In overall population, the median disease-free survival (DFS) was improved in PORT arm compared to non-PORT arm (22.9 vs. 16.1 months; p = 0.036), along with higher 2-year locoregional recurrence-free survival (LRFS) rate (88.3% vs. 69.3%; p = 0.004). In EGFR wild-type patients, PORT was associated with a longer median DFS (23.3 vs. 17.2 months; p = 0.044), and a higher 2-year LRFS rate (86.8% vs. 61.9%; p = 0.012). In EGFR mutant patients, PORT was not significantly correlated with improved survival outcomes. EGFR wild-type may a biomarker to identify the cohort that benefits from PORT.

Prevalence of mental health symptoms and associated risk factors among healthcare workers in specialized COVID-19 hospitals in Anyang, China: A cross-sectional survey.

Background: The novel coronavirus disease 2019 (COVID-19) pandemic spread worldwide and brought unprecedented challenges to healthcare systems. Healthcare workers experienced tremendous pressure and psychological issues. Methods: A cross-sectional online survey was conducted from January 2022 to April 2022 among healthcare workers in Anyang, Henan Province, China. Insomnia, anxiety, depression, post-traumatic stress disorder (PTSD), and problematic internet use (PIU) were evaluated. Logistic regression analyses were used to explore the factors that were associated with mental health problems. Results: A total of 242 participants (mean [SD] age, 34.7 [6.6] years, 187 female [77.3 %]) were included in the study. The prevalence of symptoms of insomnia, anxiety, depression, PTSD and PIU during the COVID-19 pandemic in China was 53.7 %, 100.0 %, 7.0 %, 20.3 %, and 19.4 %, respectively. Participants who smoked, used sedative-hypnotic drugs and may need psychological assistance were at a higher risk for mental health problems. Respondents who were older than 45 years and were married displayed a lower risk of insomnia and PTSD, respectively. Conclusions: Mental health symptoms are pervasive among healthcare workers in specialized COVID-19 hospitals during the outbreak. Risk factors include smoking, sedative-hypnotic drug use, and the need for psychological assistance, while protective factors include age and marital status. Developing social media platforms and providing psychological assistance may be effective interventions for healthcare workers.

Morphological characteristics and phylogenetic analyses revealed four new wood inhabiting fungi (Agaricomycetes, Basidiomycota) in Xizang Autonomous Region, China.

Four new fungi from Xizang in southwest China, Caloceraramaria, Ceraceomycesrhizomorphus, Leptosporomyceslinzhiensis, and Ramariaxizangensis are described and illustrated based on the morphological and molecular evidence. Caloceraramaria is characterized by the ramal and bright orange basidiomata, a monomitic hyphal system with simple septa generative hyphae, usually 4-septate basidiospores; Ceraceomycesrhizomorphus is characterized by the cream to yellowish basidiomata with rhizomorphs, cylindrical basidiospores; Leptosporomyceslinzhiensis is characterized by white with pink basidiomata, cylindrical to oblong ellipsoid basidiospores; Ramariaxizangensis is characterized by flesh pink basidiomata, branched dichotomously in 4-5 ranks, a monomitic hyphal system with clamped generative hyphae, ellipsoid to cylindrical and densely warted basidiospores.

Malignant myopericytoma originating from the colon: A case report.

BACKGROUND: Myopericytoma is a benign tumor that typically occurs within subcutaneous tissue and most often involves the distal extremities, followed by the proximal extremities, neck, thoracic vertebrae and oral cavity. Complete resection is often curative. Malignant myopericytoma is extremely rare and has a poor prognosis. Here, we report for the first time a case of malignant myopericytoma originating from the colon. CASE SUMMARY: A 69-year-old male was admitted to our hospital with right upper quadrant pain for five days. Imaging suggested a liver mass with hemorrhage. A malignant hepatic tumor was the initial diagnosis. Surgical resection was performed after a complete preoperative work up. Initial postoperative pathology suggested that the mass was a malignant myoblastoma unrelated to the liver. Four months after the first surgery, an enhanced computed tomography (CT) scan revealed a recurrence of the tumor. The diagnosis of malignant myopericytoma derived from the colon was confirmed on histopathological examination of the specimen from the second surgery. The patient did not return to the hospital regularly for surveillance. The first postoperative abdominal CT examination six months after the second surgery demonstrated multiple liver metastases. Survival time between the diagnosis of the tumor to death was approximately one year. CONCLUSION: Malignant myopericytoma is a rare cancer. Preoperative diagnosis may be difficult. Due to a lack of treatment options, prognosis is poor.

Using rDNA ITS2 barcoding to identify kratom (Mitragyna speciosa) from the genus Mitragyna and Neolamarckia cadamba.

This study collected 80 samples of suspected kratom plant powder. A polymerase chain reaction sequence analysis was conducted using two sets of DNA barcode primers for plant ribosomal (r)DNA internal transcribed spacers (ITSs), namely, ITS3/ITS4 and ITS-p3/ITS-u4. Among the 80 samples, 40 were analyzed using the ITS3/ITS4 primer pair, and then DNA sequences were subjected to a National Center for Biotechnology Information-Basic Local Alignment Search Tool (NCBI-BLAST) comparison. Results showed that 29 samples had a 100% match (364/364) with Mitragyna speciosa (kratom), and 6 samples had a 99.73% match (363/364) with M. speciosa, whereas 5 samples had disordered and unreadable sequences. The 5 unreadable samples and an additional 40 suspected kratom samples were then analyzed using the ITS-p3/ITS-u4 primer pair, followed by an NCBI-BLAST comparison. Among these, 32 samples had a 100% match (404/404) with M. speciosa, and 11 samples had a 99.75% match (403/404) with M. speciosa. Among the samples with sequences matching M. speciosa, three distinct types were observed (no variance/404, 287M/404, and 287A/404). One sample had a 99.51% match (404/406) with Neolamarckia cadamba, and another sample had a sequencing length of 305 bp, with 25 positions showing mixed base pairs, indicating a mixture of different species. Analysis of the mixed base pair pattern suggested a possible mixture of M. speciosa and N. cadamba. Actually, M. speciosa and N. cadamba have very similar external morphologies. This indicates that the ITS-p3/ITS-u4 primer pair is effective in distinguishing mixtures of M. speciosa and N. cadamba and is thus more suitable than ITS3/ITS4 for identifying and analyzing samples of suspected kratom plant powder.

Mosaic distal 9p deletion or 46,XY,del(9)(p23)/46,XY at amniocentesis in a pregnancy associated with perinatal progressive decrease of the aneuploid cell line and a favorable fetal outcome.

OBJECTIVE: We present mosaic distal 9p deletion at prenatal diagnosis in a pregnancy associated with a favorable fetal outcome. CASE REPORT: A 34-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY, del(9)(p23)[8]/46,XY[17]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes showed 43% mosaicism for the 9p24.3p23 deletion. Prenatal ultrasound suspected hypospadias and echogenic bowel. At 23 weeks of gestation, she was referred for genetic counseling, and repeat amniocentesis revealed a karyotype of 46,XY,del(9)(p23)[10]/46,XY[10]. The parental karyotypes were normal. Molecular genetic analysis on uncultured amniocytes revealed no uniparental disomy (UPD) 9 by quantitative fluorescence polymerase chain reaction (QF-PCR) and arr 9p24.3p23 × 1.55 (40%-50% mosaicism) by aCGH. At 27 weeks of gestation, she underwent the third amniocentesis which revealed a karyotype of 46,XY,del(9)(p23)[6]/46,XY[14]. Simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed the result of arr 9p24.3p23 (35% mosaicism). Prenatal ultrasound was normal. She was advised to continue the pregnancy, and a 3020-g phenotypically normal male baby was delivered at 41 weeks of gestation. At birth, the karyotypes of cord blood, umbilical cord and placenta were 46,XY,del(9)(p23)[7]/46,XY[37], 46,XY,del(9)(p23)[17]/46,XY[23] and 46,XY in 40/40 cells, respectively. When follow-up at age three months, the neonate was normal in phenotype and development. The peripheral blood had a karyotype of 46,XY,del(9)(p23)[3]/46,XY[37], and interphase fluorescence in situ hybridization (FISH) analysis on buccal mucosal cells showed 13% (13/102 cells) mosaicism for the distal 9p deletion. CONCLUSION: Mosaic distal 9p deletion with a normal cell line at prenatal diagnosis can be associated with a favorable fetal outcome and perinatal progressive decrease of the aneuploid cell line.

Low-level mosaic trisomy 7 at amniocentesis in a pregnancy associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, perinatal progressive decrease of the trisomy 7 cell line and a favorable fetal outcome.

OBJECTIVE: We present low-level mosaic trisomy at amniocentesis in a pregnancy associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, perinatal progressive decrease of the trisomy 7 cell line and a favorable fetal outcome. CASE REPORT: A 40-year-old, primigravid woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY in cultured amniocytes. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (7) × 2-3, (X,Y) × 1, consistent with 24% mosaicism for trisomy 7. Polymorphic DNA marker analysis on the DNA extracted from the uncultured amniocytes and parental bloods excluded uniparental disomy (UPD) 7. Prenatal ultrasound findings were normal. She was referred for genetic counseling at 19 weeks of gestation. No repeat amniocentesis was suggested, and continuing the pregnancy was advised. At 22 weeks of gestation, the result of soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) = 6.1 (normal < 38). She did not have preeclampsia. At 39 weeks of gestation, a 3346-g male baby was delivered without any phenotypic abnormality. aCGH analysis on the DNA extracted from cord blood and placenta revealed the result of arr (1-22) × 2, (X,Y) × 1 with no genomic imbalance in all tissues. When follow-up at age three months, the baby was normal in development and phenotype. The peripheral blood had a karyotype of 46,XY, and interphase fluorescence in situ hybridization (FISH) analysis using the bacterial artificial chromosome (BAC) probes of chromosome 7 showed disomy 7 cells in all 102/102 cells. CONCLUSION: Low-level mosaic trisomy 7 at amniocentesis can be associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, perinatal progressive decrease of the trisomy 7 cell line and a favorable fetal outcome.

Prenatal diagnosis of familial 3p26.3p25.3 deletion in a pregnancy associated with a favorable fetal outcome and asymptomatic carrier parent and family members in three generations.

OBJECTIVE: We present prenatal diagnosis of familial 3p26.3p25.3 deletion in a pregnancy associated with a favorable fetal outcome and asymptomatic carrier parent and family members in three generations. CASE REPORT: A 35-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age and the carrier of distal 3p deletion. She was phenotypically normal, and there was no family history of congenital anomalies. Amniocentesis revealed a karyotype of 46,XY,del(3)(p26.1). Repeat amniocentesis at 21 weeks of gestation revealed a karyotype of 46,XY,del(3)(p25.3). Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes showed the result of arr 3p26.3p25.3 (117,735-8,709,972) × 1.0 [GRCh37 (hg19)] with an 8.59-Mb deletion of 3p26.3p25.3 encompassing 14 OMIM genes of CHL1, CNTN6, CNTN4, IL5RA, TRNT1, CRBN, SETMAR, SUMF1, ITPR1, BHLHE40, ARL8B, GRM7, LMCD1 and SSUH2. Cytogenetic analysis of parental bloods revealed a karyotype of 46,XX,del (3) (p25.3) in the mother and 46,XY in the father. The woman's 69-year-old mother and her 2-year-old elder son carried the same aberrant chromosome of 3p25.3→p26.3 deletion by conventional cytogenetic analysis but manifested no phenotypic abnormality. aCGH analysis of the peripheral bloods showed that the woman's mother and her elder son had the same 8.59-Mb deletion of 3p26.3p25.3. The woman was advised to continue the pregnancy. At 39 weeks of gestation, a 3040-g healthy male baby was delivered. When follow-up at age 2½ years, the neonate was normal in development and showed no apparent phenotypic abnormality. CONCLUSION: Distal 3p deletion of 3p26.3p25.3 involving the OMIM genes from CHL1 to SSUH2 can be associated with no apparent phenotypic abnormality.

A survey of generative AI for de novo drug design: new frontiers in molecule and protein generation.

Artificial intelligence (AI)-driven methods can vastly improve the historically costly drug design process, with various generative models already in widespread use. Generative models for de novo drug design, in particular, focus on the creation of novel biological compounds entirely from scratch, representing a promising future direction. Rapid development in the field, combined with the inherent complexity of the drug design process, creates a difficult landscape for new researchers to enter. In this survey, we organize de novo drug design into two overarching themes: small molecule and protein generation. Within each theme, we identify a variety of subtasks and applications, highlighting important datasets, benchmarks, and model architectures and comparing the performance of top models. We take a broad approach to AI-driven drug design, allowing for both micro-level comparisons of various methods within each subtask and macro-level observations across different fields. We discuss parallel challenges and approaches between the two applications and highlight future directions for AI-driven de novo drug design as a whole. An organized repository of all covered sources is available at https://github.com/gersteinlab/GenAI4Drug.

Berberine ameliorates vascular dysfunction by downregulating TMAO-endoplasmic reticulum stress pathway via gut microbiota in hypertension.

The gut microbial metabolite trimethylamine N-oxide (TMAO) is regarded as a novel risk factor for hypertension. Berberine (BBR) exerts cardiovascular protective effects by regulating the gut microbiota-metabolite production pathway. However, whether and how BBR alleviates TMAO-induced vascular dysfunction in hypertension remains unclear. In the present study, we observed that plasma TMAO and related bacterial abundance were significantly elevated and negatively correlated with vascular function in 86 hypertensive patients compared with 46 normotensive controls. TMAO activated endoplasmic reticulum stress (ERS) signaling pathway to promote endothelial cell dysfunction and apoptosis in vitro. BBR (100, 200 mg ·â€¯kg-1 ·d-1) for 4 weeks ameliorates TMAO-induced vascular dysfunction and ERS activation in a choline-angiotensin II hypertensive mouse model. We found that plasma TMAO levels in 15 hypertensive patients treated with BBR (0.4 g, tid) were reduced by 8.8 % and 16.7 % at months 1 and 3, respectively, compared with pretreatment baseline. The oral BBR treatment also improved vascular function and lowered blood pressure. Faecal 16 S rDNA showed that BBR altered the gut bacterial composition and reduced the abundance of CutC/D bacteria in hypertensive mice and patients. In vitro bacterial cultures and enzyme reaction systems indicated that BBR inhibited the biosynthesis of TMAO precursor in the gut microbiota by binding to and inhibiting the activity of CutC/D enzyme. Our results indicate that BBR improve vascular dysfunction at least partially by decreasing TMAO via regulation of the gut microbiota in hypertension.

Unraveling the assembly mechanism of SADS-CoV virus nucleocapsid protein: insights from RNA binding, dimerization, and epitope diversity profiling.

The swine acute diarrhea syndrome coronavirus (SADS-CoV) has caused significant disruptions in porcine breeding and raised concerns about potential human infection. The nucleocapsid (N) protein of SADS-CoV plays a vital role in viral assembly and replication, but its structure and functions remain poorly understood. This study utilized biochemistry, X-ray crystallography, and immunization techniques to investigate the N protein's structure and function in SADS-CoV. Our findings revealed distinct domains within the N protein, including an RNA-binding domain, two disordered domains, and a dimerization domain. Through biochemical assays, we confirmed that the N-terminal domain functions as an RNA-binding domain, and the C-terminal domain is involved in dimerization, with the crystal structure analysis providing visual evidence of dimer formation. Immunization experiments demonstrated that the disordered domain 2 elicited a significant antibody response. These identified domains and their interactions are crucial for viral assembly. This comprehensive understanding of the N protein in SADS-CoV enhances our knowledge of its assembly and replication mechanisms, enabling the development of targeted interventions and therapeutic strategies. IMPORTANCE: SADS-CoV is a porcine coronavirus that originated from a bat HKU2-related coronavirus. It causes devastating swine diseases and poses a high risk of spillover to humans. The coronavirus N protein, as the most abundant viral protein in infected cells, likely plays a key role in viral assembly and replication. However, the structure and function of this protein remain unclear. Therefore, this study employed a combination of biochemistry and X-ray crystallography to uncover distinct structural domains in the N protein, including RNA-binding domains, two disordered domains, and dimerization domains. Additionally, we made the novel discovery that the disordered domain elicited a significant antibody response. These findings provide new insights into the structure and functions of the SADS-CoV N protein, which have important implications for future studies on SADS-CoV diagnosis, as well as the development of vaccines and anti-viral drugs.

Rapid, sensitive, and visual detection of pseudorabies virus with an RPA-CRISPR/EsCas13d-based dual-readout portable platform.

Pseudorabies viruses (PRV) pose a major threat to the global pig industry and public health. Rapid, intuitive, affordable, and accurate diagnostic testing is critical for controlling and eradicating infectious diseases. In this study, a portable detection platform based on RPA-CRISPR/EsCas13d was developed. The platform exhibits high sensitivity (1 copy/µL), good specificity, and no cross-reactivity with common pathogens. The platform uses rapid preamplification technology to provide visualization results (lateral flow assays or visual fluorescence) within 1 h. Fifty pig samples (including tissues, oral fluids, and serum) were tested using this platform and real-time quantitative polymerase chain reaction (qPCR), showing 34.0 % (17 of 50) PRV positivity with the portable CRISPR/EsCas13d dual-readout platform, consistent with the qPCR results. These results highlight the stability, sensitivity, efficiency, and low equipment requirements of the portable platform. Additionally, a novel point-of-care test is being developed for clinical use in remote rural and resource-limited areas, which could be a prospective measure for monitoring the progression of pseudorabies and other infectious diseases worldwide.