Inhibitory activities of five fungicides on Alternaria suffruticosae and their field control efficacy against tree peony black spot.

Tree peony black spot (TPBS), mainly caused by Alternaria suffruticosae, is a common leaf disease on the ornamental peony, which posed a great threat on the flower buds in the current year and the flowering quality in the next year. However, there was only one fungicide registered for the control of the disease, difenoconazole. In order to avoid the severe problem of pathogen resistance caused by long-term use of difenoconazole, it is necessary to screen more chemical fungicides for the prevention and control of TPBS. In the paper, the biological activities of flutolanil, phenamacril, pyraclostrobin, and boscalid on mycelial growth, conidial germination, germ tube elongation and sporulation quantity of A. suffruticosae were determined, and field control efficacy were conducted to evaluate the preventive and therapeutic activities. Difenoconazole, was used as a control simultaneously. The results showed that pyraclostrobin had the strongest inhibitory effects on the conidial germination, mycelium growth, germ tube elongation and sporulation quantity, with the average EC50 of 0.0517, 0.5343, 0.0008 and 0.8068 µg/mL respectively. The inhibitory activity of flutolanil on the four developmental stages of A. suffruticosae was weaker than the other three fungicides. Compared with flutolanil, boscalid, the other succinate dehydrogenase inhibitors, had more srtong inhibitory effects on the mycelial growth and sporulation quantity, with the average EC50 of 3.8603 and 1.4760 µg/mL respectively. Phenamacril had a moderate inhibitory level, which had more inhibitory activity on conidial germination and germ tube elongation, with the average EC50 of 31.5349 and 5.2597 µg/mL. All of the four fungicides had no significant effects on the shape of spores and germ tubes. The control fungicide difenoconazole had the strongest inhibitory activity on mycelial growth, and the average EC50 was only 0.3297 µg/ml. However, its inhibitory activity on the other three growth stages was not high. In the field trials, pyraclostrobin had high control efficacy on TPBS even at low concentrations, reaching a minimum of 62.6293%, which was higher than that of difenoconazole. The other three fungicides had higher control efficacy at high concentrations, but decreased significantly at low concentrations. Considering the dosage and control efficacy, pyraclostrobin was the first choice for the control of TPBS. Pyraclostrobin is the preferred alternative fungicide of difenoconazole for the prevention and control of TPBS in production.

Dihydroquercetin regulates HIF-1α/AKT/NR2B signalling to improve impaired brain function in rats with metabolic syndrome.

Dihydroquercetin (DHQ) is commonly used as a dietary additive, but its activity in improving brain injury with metabolic syndrome (MS) remains known. In present study, the MS rat model was induced using 10 % fructose water. The apoptosis rate of primary brain cells was detected. The HIF-1α/AKT/NR2B signalling pathway, levels of KEAP1/NRF2, HO-1 and NQO-1 were detected. In vitro experiments were performed using H2O2-stimulated PC-12 cells. The effect of DHQ on rates of cell survival and apoptosis were detected. After silencing HIF-1α, we further elucidate the mechanism of action of DHQ. The results indicated that DHQ reduced the hyperactivity and inhibited oxidative stress via increasing the levels of HIF-1α/AKT/NR2B signalling pathway, whereas regulated KEAP1/NRF2 pathway. In vitro experiments showed that the HIF-1α plays an important role in this process. Overall, DHQ may improve impaired brain function in rats with metabolic syndrome by regulating the HIF-1α/AKT/NR2B signalling pathway.

Prototype-based sample-weighted distillation unified framework adapted to missing modality sentiment analysis.

Missing modality sentiment analysis is a prevalent and challenging issue in real life. Furthermore, the heterogeneity of multimodality often leads to an imbalance in optimization when attempting to optimize the same objective across all modalities in multimodal networks. Previous works have consistently overlooked the optimization imbalance of the network in cases when modalities are absent. This paper presents a Prototype-Based Sample-Weighted Distillation Unified Framework Adapted to Missing Modality Sentiment Analysis (PSWD). Specifically, it fuses features with a more efficient transformer-based cross-modal hierarchical cyclic fusion module. Subsequently, we propose two strategies, namely sample-weighted distillation and prototype regularization network, to address the issues of missing modality and optimization imbalance. The sample-weighted distillation strategy assigns higher weights to samples that are located closer to class boundaries. This facilitates the obtaining of complete knowledge by the student network from the teacher's network. The prototype regularization network calculates a balanced metric for each modality, which adaptively adjusts the gradient based on the prototype cross-entropy loss. Unlike conventional approaches, PSWD not only connects the sentiment analysis study in the missing modality to the full modality, but the proposed prototype regularization network is not reliant on the network structure and can be expanded to more multimodal studies. Massive experiments conducted on IEMOCAP and MSP-IMPROV show that our method achieves the best results compared to the latest baseline methods, which demonstrates its value for application in sentiment analysis.

Streamflow seasonality in a snow-dwindling world.

Climate warming induces shifts from snow to rain in cold regions1, altering snowpack dynamics with consequent impacts on streamflow that raise challenges to many aspects of ecosystem services2-4. A straightforward conceptual model states that as the fraction of precipitation falling as snow (snowfall fraction) declines, less solid water is stored over the winter and both snowmelt and streamflow shift earlier in season. Yet the responses of streamflow patterns to shifts in snowfall fraction remain uncertain5-9. Here we show that as snowfall fraction declines, the timing of the centre of streamflow mass may be advanced or delayed. Our results, based on analysis of 1950-2020 streamflow measurements across 3,049 snow-affected catchments over the Northern Hemisphere, show that mean snowfall fraction modulates the seasonal response to reductions in snowfall fraction. Specifically, temporal changes in streamflow timing with declining snowfall fraction reveal a gradient from earlier streamflow in snow-rich catchments to delayed streamflow in less snowy catchments. Furthermore, interannual variability of streamflow timing and seasonal variation increase as snowfall fraction decreases across both space and time. Our findings revise the 'less snow equals earlier streamflow' heuristic and instead point towards a complex evolution of seasonal streamflow regimes in a snow-dwindling world.

Different biomarker ratios in peripheral blood have limited value in diagnosing periprosthetic joint infection after total joint arthroplasty: a single-center, retrospective study.

BACKGROUND: Periprosthetic joint infection (PJI) is a severe complication that can occur after total joint arthroplasty (TJA). The timely and accurate diagnosis of PJI is the key to treatment. This study investigated the diagnostic value of platelet to lymphocyte ratio (PLR), platelet count to mean platelet volume ratio (PVR), neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) in PJI after total knee arthroplasty (TKA) and total hip arthroplasty (THA). METHODS: We performed a retrospective analysis of the patients who underwent revision hip or knee arthroplasty at our Institute between June 2015 and June 2020. Of the 187 patients reviewed, 168 were included in the study. According to the diagnostic criteria of the Musculoskeletal Infection Society (MSIS), 58 patients were in the PJI group, and 110 patients were in the aseptic loosening (AL) group. We recorded and compared the preoperative peripheral blood white blood cell (WBC) count, platelet count (PLT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), PLR, PVR, NLR, and MLR in both groups. The diagnostic performance of the WBC, PLT, PLR, PVR, NLR, and MLR individually and in combination with the ESR and CRP for PJI diagnosis was evaluated by receiver operating characteristic (ROC) curves, and the sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: Compared to those in the AL group, the mean WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR in the peripheral blood of the PJI group were significantly greater (P < 0.05). The analysis of the ROC curve revealed that the ESR, CRP, PLR, PVR, NLR, and MLR in peripheral blood had moderate effectiveness in diagnosing PJI, with area under the curve (AUC) values of 0.760 (95% CI: 0.688-0.823), 0.758 (95% CI: 0.687-0.821), 0.714 (95% CI: 0.639-0.781), 0.709 (95% CI: 0.634-0.777), 0.723 (95% CI: 0.649-0.789), and 0.728 (95% CI: 0.654-0.793), respectively. Conversely, the WBC and PLT counts demonstrated poor diagnostic value for PJI, with AUC values of 0.578 (95% CI: 0.499-0.653) and 0.694 (95% CI: 0.619-0.763), respectively. The results of the prediction model calculations revealed that the combined AUC of the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR was the highest at 0.853 (95% CI, 0.790-0.909), indicating good value in the diagnosis of PJI, with a sensitivity of 82.8% and a specificity of 72.7%. Moreover, the novel composite of parameters improved the accuracy and reliability in diagnosing PJI compared to the traditional biomarkers ESR and CRP (P = 0.015). CONCLUSION: Our study suggested that the diagnostic value of the peripheral blood biomarkers PLR, PVR, NLR, and MLR for diagnosing PJI is limited and not superior to that of the ESR or CRP. However, when the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR are combined, the diagnostic performance of PJI in TJA patients can be improved.

Adverse childhood experience and depression: the role of gut microbiota.

Depression is the most common psychiatric disorder that burdens modern society heavily. Numerous studies have shown that adverse childhood experiences can increase susceptibility to depression, and depression with adverse childhood experiences has specific clinical-biological features. However, the specific neurobiological mechanisms are not yet precise. Recent studies suggest that the gut microbiota can influence brain function and behavior associated with depression through the "microbe-gut-brain axis" and that the composition and function of the gut microbiota are influenced by early stress. These studies offer a possibility that gut microbiota mediates the relationship between adverse childhood experiences and depression. However, few studies directly link adverse childhood experiences, gut microbiota, and depression. This article reviews recent studies on the relationship among adverse childhood experiences, gut microbiota, and depression, intending to provide insights for new research.

Short-homology-mediated PCR-based method for gene introduction in the fission yeast Schizosaccharomyces pombe.

Schizosaccharomyces pombe is a commonly utilized model organism for studying various aspects of eukaryotic cell physiology. One reason for its widespread use as an experimental system is the ease of genetic manipulations, leveraging the natural homology-targeted repair mechanism to accurately modify the genome. We conducted a study to assess the feasibility and efficiency of directly introducing exogenous genes into the fission yeast S. pombe using Polymerase Chain Reaction (PCR) with short-homology flanking sequences. Specifically, we amplified the NatMX6 gene (which provides resistance to nourseothricin) using PCR with oligonucleotides that had short flanking regions of 20 bp, 40 bp, 60 bp and 80 bp to the target gene. By using this purified PCR product, we successfully introduced the NatMX6 gene at position 171 385 on chromosome III in S. pombe. We have made a simple modification to the transformation procedure, resulting in a significant increase in transformation efficiency by at least 5-fold. The success rate of gene integration at the target position varied between 20% and 50% depending on the length of the flanking regions. Additionally, we discovered that the addition of dimethyl sulfoxide and boiled carrier DNA increased the number of transformants by ~60- and 3-fold, respectively. Furthermore, we found that the removal of the pku70+ gene improved the transformation efficiency to ~5% and reduced the formation of small background colonies. Overall, our results demonstrate that with this modified method, even very short stretches of homologous regions (as short as 20 bp) can be used to effectively target genes at a high frequency in S. pombe. This finding greatly facilitates the introduction of exogenous genes in this organism.

Understanding Macrophage-Tumor Interactions: Insights from Single-Cell Behavior Monitoring in a Sessile Microdroplet System.

Interaction between tumor-associated macrophages and tumor cells is crucial for tumor development, metastasis, and the related immune process. However, the macrophages are highly heterogeneous spanning from anti-tumorigenic to pro-tumorigenic, which needs to be understood at the single-cell level. Herein, a sessile microdroplet system designed for monitoring cellular behavior and analyzing intercellular interaction, demonstrated with macrophage-tumor cell pairs is presented. An automatic procedure based on the inkjet printing method is utilized for the precise pairing and co-encapsulation of heterotypic cells within picoliter droplets. The sessile nature of microdroplets ensures controlled fusion and provides stable environments conducive to adherent cell culture. The nitric oxide generation and morphological changes over incubation are explored to reveal the complicated interactions from a single-cell perspective. The immune response of macrophages under distinct cellular microenvironments is recorded. The results demonstrate that the tumor microenvironment displays a modulating role in polarizing macrophages from anti-tumorigenic into pro-tumorigenic phenotype. The approach provides a versatile and compatible platform to investigate intercellular interaction at the single-cell level, showing promising potential for advancing single-cell behavior studies.

Longitudinal analysis of liver transplant candidates for hepatocellular carcinoma in a single center.

BACKGROUND: Wailitst lost is an critical issue and we investigated the long-term effect of insufficient liver functional reserve at liver transplantation evaluation on waitlist outcomes in patients with hepatocellular carcinoma (HCC). METHODS: Clinical data of patients with HCC waitlisted for liver transplantation were retrospectively collected from a single hospital cohort during the period from 2014 to 2021. Parameters of liver reserve, including cirrhosis, Child-Pugh grade, and Model for End-Stage Liver Disease (MELD) scores, were analyzed for patient survival, after adjustment for tumor factors. RESULTS: Of 292 eligible patients, 94.2% had cirrhosis, 55.8% had Child-Pugh grade B or C, and the median MELD score was 13.2. The median follow-up time was 2.2 years, with a dropout rate of 62.7%. Eighty-nine candidates (30.5%) eventually received liver transplant, including 67 from live donors. The estimated 1-year mortality rate reached 40.6% in 203 patients who remained on the waitlist without receiving a transplant, of whom 143 died. Most deaths were attributed to liver failure (37.1%) and cancer death (35.7%). After we adjusted for tumor confounders, including alpha fetoprotein, primary HCC stage, tumor number at evaluation, and sequential cancer treatment before and while waiting, hazard ratios (HRs) for patient survival were 1.69 (95% confidence interval, 1.18-2.41) for cirrhotic stage B or C, 1.07 (1.04-1.10) for MELD scores, and 1.14 (1.04-1.25) for tumor size at transplant evaluation. Transplantation was a protective disease modifier with adjusted HR 0.22 (0.14-0.33). CONCLUSION: Insufficient liver functional reserve poses more risk than expected to liver transplant waitlist outcomes with HCC.

Relationship between changes in neurological deficit severity and adverse cardiac events in elderly patients with hypertensive intracerebral hemorrhage: a retrospective cohort study.

OBJECTIVE: To explore the relationship between changes in neurological deficit severity and the occurrence of adverse cardiac events in elderly patients with hypertensive intracerebral hemorrhage. METHODS: Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of NIHSS scores for adverse cardiac events. RESULTS: There were significant differences between the two groups. Multivariate logistic regression analysis showed that advanced age, high NIHSS score, large intracerebral hemorrhage volume, and high CK level were independent risk factors for adverse cardiac events in elderly patients with hypertensive intracerebral hemorrhage (p < 0.05). The NIHSS scores of both groups gradually increased after admission, peaking at 48 h after admission. In Group A, this elevation persisted until 72 h after admission, while in Group B, there was a significant decrease at 72 h after admission (p < 0.05). From admission to 7 days after admission, the NIHSS scores in Group A were higher than those in Group B (p < 0.05). The area under the curve (AUC) of the NIHSS scores at 48 h after admission was 0.776, with sensitivity and specificity of 80.9% and 84.5%, respectively, which were higher than those of other indicators (p < 0.05). CONCLUSION: The occurrence of adverse cardiac events in elderly patients with hypertensive intracerebral hemorrhage is influenced by multiple factors, and as the NIHSS score increases, the risk of such events gradually increases. Clinicians should pay attention to monitoring NIHSS scores after admission, as they have value in predicting adverse cardiac events in elderly patients with hypertensive intracerebral hemorrhage.

Genome-Wide Identification, Expression Analysis under Abiotic Stress and Co-Expression Analysis of MATE Gene Family in Torreya grandis.

The multidrug and toxin efflux (MATE) family participates in numerous biological processes and plays important roles in abiotic stress responses. However, information about the MATE family genes in Torreya grandis remains unclear. In this study, our genome-wide investigation identified ninety MATE genes in Torreya grandis, which were divided into five evolutionary clades. TgMATE family members are located on eleven chromosomes, and a total of thirty TgMATEs exist in tandem duplication. The promoter analysis showed that most TgMATEs contain the cis-regulatory elements associated with stress and hormonal responses. In addition, we discovered that most TgMATE genes responded to abiotic stresses (aluminum, drought, high temperatures, and low temperatures). Weighted correlation network analysis showed that 147 candidate transcription factor genes regulated the expression of 14 TgMATE genes, and it was verified through a double-luciferase assay. Overall, our findings offer valuable information for the characterization of the TgMATE gene mechanism in responding to abiotic stress and exhibit promising prospects for the stress tolerance breeding of Torreya grandis.

Mesenchymal stem cell-derived exosomes overexpressing SRC-3 protect mice from cerebral ischemia by inhibiting ferroptosis.

BACKGROUND: The treatment for cerebral ischemia remains limited, and new therapeutic strategies are urgently needed. Exosome has shown great promise for the treatment of cerebral ischemia. Steroid receptor coactivator-3 (SRC-3) was reported to be involved in neurological performances. In this study, we aimed to investigate the protective effects of mesenchymal stem cell (MSC)-derived exosomes overexpressing SRC-3 on cerebral ischemia in mice. METHODS: The mice were treated with an intracerebroventricular injection of GFP-overexpressed exosomes (GFP-exo) and SRC-3-overexpressed exosomes (SRC3-exo) in a middle cerebral artery occlusion (MCAO) model of cerebral ischemia. RESULTS: The results showed that SRC3-exo treatment significantly inhibited lipid peroxidation and ferroptosis of the neurons subjected to oxygen-glucose deprivation. It further suppressed the activation of microglia and astrocytes, and decreased the production of pro-inflammatory cytokines in the brains of MCAO mice. Furthermore, SRC3-exo treatment reduced the water content of brain tissue and infarct size, which alleviated the neurological damage and improved neurological performances in the MCAO mice. CONCLUSIONS: Our results suggest that MSC-derived exosomes expressing SRC3 can be a therapeutic strategy for cerebral ischemia by inhibiting ferroptosis.

Chromium immobilization from wastewater via iron-modified hydrochar: Different iron fabricants and practicality assessment.

The recycling of industrial solid by-products such as red mud (RM) has become an urgent priority, due to their large quantities and lack of reutilization methods can lead to resource wastage. In this work, RM was employed to fabricate green hydrochar (HC) to prepare zero-valent iron (ZVI) modified carbonous materials, and conventional iron salts (IS, FeCl3) was applied as comparison, fabricated HC labeled as RM/HC and IS/HC, respectively. The physicochemical properties of these HC were comprehensively characterized. Further, hexavalent chromium (Cr(VI)) removal performance was assessed (375.66 and 337.19 mg/g for RM/HC and IS/HC, respectively). The influence of dosage and initial pH were evaluated, while isotherms, kinetics, and thermodynamics analysis were also conducted, to mimic the surface interactions. The stability and recyclability of adsorbents also verified, while the practical feasibility was assessed by bok choy-planting experiment. This work revealed that RM can be used as a high value and green fabricant for HC the effective removal of chromium contaminants from the wastewater.

Risk factors, patterns, and outcome predictors of late recurrence in patients with hepatocellular carcinoma after curative resection: A large cohort study with long-term follow-up results.

BACKGROUND: Late recurrence of hepatocellular carcinoma after curative resection significantly influences long-term patient survival outcomes, and yet it remains understudied. This study aims to explore the risk factors and patterns of late recurrence and predictors of subsequent outcome. METHODS: This single-center retrospective study analyzed 1,701 consecutive patients who achieved a disease-free survival period exceeding 2 years after curative resection for hepatocellular carcinoma between 2001 and 2018. Univariate and multivariate analyses of factors associated with late recurrence and death after recurrence were conducted using Cox's models. RESULTS: The mean age of patients was 60.2 years, with 76.8% being male. During a median follow-up of 8.1 years, 653 patients (38.4%) experienced late recurrence, with median time to recurrence being 4.0 years (interquartile range, 2.7-6.0). Factors such as age >60, chronic hepatitis C, cirrhosis, high albumin-bilirubin grade, absence of family history, multiple tumors, satellite nodules, alpha-fetoprotein levels <400 ng/mL, and minor hepatic resection were identified as risk factors for late recurrence. Among patients with late recurrence, 131 (20.1%) underwent surgical treatment, 272 (41.7%) received radiofrequency ablation, and 27 (4.1%) exhibited extrahepatic lesions. A higher-high albumin-bilirubin grade, recurrent tumor >3 cm, and nonsurgical treatment emerged as predictors of death after late recurrence. CONCLUSION: Over one-third of patients who remain disease-free for more than 2 years postresection will experience late recurrence during subsequent follow-up. For 2-year disease-free survivors, risk factors for late recurrence differ from early recurrence. Treating underlying hepatitis is of paramount importance, given its association with both the risk of late recurrence and survival outcomes post-recurrence.

Deep brain stimulation of the subthalamic nucleus increases the risk of sialorrhea in patients with advanced Parkinson's disease.

INTRODUCTION: Sialorrhea is a common neurological manifestation of Parkinson's disease (PD). No specifically designed prospective study has tested the effects of deep brain stimulation of the subthalamic nucleus (STN-DBS) on sialorrhea in patients with advanced PD. We focused on the effect of STN-DBS on the incidence of sialorrhea in patients with PD. METHODS: This multicenter, prospective, non-randomized concurrent clinical trial analyzed the incidence of sialorrhea during long-term follow-up in 170 patients with advanced PD (84 patients with STN-DBS and 86 patients with medication therapy). RESULTS: After STN-DBS, 58.1% of patients presented with sialorrhea (Drooling Rating Scale (DRS) > 5) compared with 39.3% of patients with medication therapy (P < 0.001). STN-DBS stimulation demonstrated a significant increase in DRS and Drooling Severity and Frequency Scale (DSFS) compared with the patients with medication therapy (P < 0.001). At follow-up, the onabotulinumtoxin-A (BTX-A) injection ratio was significantly higher in the STN-DBS group (29.8% vs. 11.9%, P = 0.0057) compared with the patients with medication therapy. CONCLUSIONS: STN-DBS increased the risk of sialorrhea in patients with advanced PD. TRIAL REGISTRATION: clinicaltrials. gov (NCT06090929).

Myofascial edema of gastrocnemius: A prominent MRI characteristic in dermatomyositis patients with anti-transcriptional intermediate factor 1-γ antibody.

AIMS: This study was designed to evaluate the magnetic resonance imaging (MRI) patterns of the lower limb muscles in dermatomyositis (DM) with anti-transcriptional intermediate factor 1-γ (anti-TIF1-γ) antibody. METHODS: This retrospective, observational, cross-sectional study enrolled 12 adult DM patients with anti-TIF1-γ antibody. Muscles were assessed for fascial edema, subcutaneous-tissue edema, muscle edema, and fatty replacement. These features were analyzed in relation to clinical characteristics. RESULTS: All 12 patients underwent hip and thigh MRI, and 8 completed calf MRI. All patients showed myofascial edema, muscle edema, and fatty replacement, and 8 out of 12 further exhibited subcutaneous-tissue edema. Specifically, myofascial edema of the gastrocnemius was observed in all patients (8/8). The vastus intermedialis and vastus lateralis muscles showed the most severe muscle edema, whereas the caput breve of the biceps femoris, semitendinosus, and soleus muscles exhibited the most severe fatty replacement. Although only 1 patient exhibited asymmetric muscle weakness, 9 showed asymmetric muscle edema, and 10 showed asymmetric fatty replacement. Changes in muscle edema positively correlated with creatine kinase (CK) levels. CONCLUSIONS: Myofascial edema of gastrocnemius was a prominent characteristic of anti-TIF1-γ-positive DM. Early detection of muscle edema, as well as CK levels, may be helpful for monitoring disease activity.

Clinically significant findings in a decade-long retrospective study of prenatal chromosomal microarray testing.

BACKGROUND: Chromosomal microarray (CMA) is commonly utilized in the obstetrics setting. CMA is recommended when one or more fetal structural abnormalities is identified. CMA is also commonly used to determine genetic etiologies for miscarriages, fetal demise, and confirming positive prenatal cell-free DNA screening results. METHODS: In this study, we retrospectively examined 523 prenatal and 319 products-of-conception (POC) CMA cases tested at Nationwide Children's Hospital from 2011 to 2020. We reviewed the referral indications, the diagnostic yield, and the reported copy number variants (CNV) findings. RESULTS: In our cohort, the diagnostic yield of clinically significant CNV findings for prenatal testing was 7.8% (n = 41/523) compared to POC testing (16.3%, n = 52/319). Abnormal ultrasound findings were the most common indication present in 81% of prenatal samples. Intrauterine fetal demise was the common indication identified in POC samples. The most common pathogenic finding observed in all samples was isolated trisomy 21, detected in seven samples. CONCLUSION: Our CMA study supports the clinical utility of prenatal CMA for clinical management and identifying genetic etiology in POC arrays. In addition, it provides insight to the spectrum of prenatal and POC CMA results as detected in an academic hospital clinical laboratory setting that serves as a reference laboratory.

Clinical Cytogenetics: Current Practices and Beyond.

BACKGROUND: Throughout history, the field of cytogenetics has witnessed significant changes due to the constant evolution of technologies used to assess chromosome number and structure. Similar to the evolution of single nucleotide variant detection from Sanger sequencing to next-generation sequencing, the identification of chromosome alterations has progressed from banding to fluorescence in situ hybridization (FISH) to chromosomal microarrays. More recently, emerging technologies such as optical genome mapping and genome sequencing have made noteworthy contributions to clinical laboratory testing in the field of cytogenetics. CONTENT: In this review, we journey through some of the most pivotal discoveries that have shaped the development of clinical cytogenetics testing. We also explore the current test offerings, their uses and limitations, and future directions in technology advancements. SUMMARY: Cytogenetics methods, including banding and targeted assessments like FISH, continue to hold crucial roles in cytogenetic testing. These methods offer a rapid turnaround time, especially for conditions with a known etiology involving recognized cytogenetic aberrations. Additionally, laboratories have the flexibility to now employ higher-throughput methodologies to enhance resolution for cases with greater complexity.

Dissecting the pleiotropic roles of reactive oxygen species (ROS) in lung cancer: From carcinogenesis toward therapy.

Lung cancer is a major cause of morbidity and mortality. The specific pulmonary structure to directly connect with ambient air makes it more susceptible to damage from airborne toxins. External oxidative stimuli and endogenous reactive oxygen species (ROS) play a crucial role in promoting lung carcinogenesis and development. The biological properties of higher ROS levels in tumor cells than in normal cells make them more sensitive and vulnerable to ROS injury. Therefore, the strategy of targeting ROS has been proposed for cancer therapy for decades. However, it is embarrassing that countless attempts at ROS-based therapies have had very limited success, and no FDA approval in the anticancer list was mechanistically based on ROS manipulation. Even compared with the untargetable proteins, such as transcription factors, ROS are more difficult to be targeted due to their chemical properties. Thus, the pleiotropic roles of ROS provide therapeutic potential for anticancer drug discovery, while a better dissection of the mechanistic action and signaling pathways is a prerequisite for future breakthroughs. This review discusses the critical roles of ROS in cancer carcinogenesis, ROS-inspired signaling pathways, and ROS-based treatment, exemplified by lung cancer. In particular, an eight considerations rule is proposed for ROS-targeting strategies and drug design and development.