Occurrence and characterization of viruses infecting Amorphophallus in Yunnan, China.

Viral diseases are becoming an important problem in Amorphophallus production due to the propagation of seed corms and their trade across regions. In this study, combined-High-Throughput Sequencing, RT-PCR, electron microscopy, and mechanical inoculation were used to analyze virus-like infected Amorphophallus samples in Yunnan province to investigate the distribution, molecular characterization, and diversity and evolution of Amorphophallus-infecting viruses including three isolates of dasheen mosaic virus and three orthotospoviruses: mulberry vein banding associated virus (MVBaV), tomato zonate spot virus (TZSV) and impatiens necrotic spot virus (INSV). The results showed that DsMV is the dominant virus infecting Amorphophallus, mixed infections with DsMV and MVBaV to Amorphophallus were quite common in Yunnan province, China. This is the first report on infection of Amorphophallus with MVBaV, TZSV, and impatiens necrotic spot virus (INSV) in China. This work will help to develop an effective integrated management strategy to control the spread of Amorphophallus viral diseases.

Ferroptosis-Regulated Natural Products and miRNAs and Their Potential Targeting to Ferroptosis and Exosome Biogenesis.

Ferroptosis, which comprises iron-dependent cell death, is crucial in cancer and non-cancer treatments. Exosomes, the extracellular vesicles, may deliver biomolecules to regulate disease progression. The interplay between ferroptosis and exosomes may modulate cancer development but is rarely investigated in natural product treatments and their modulating miRNAs. This review focuses on the ferroptosis-modulating effects of natural products and miRNAs concerning their participation in ferroptosis and exosome biogenesis (secretion and assembly)-related targets in cancer and non-cancer cells. Natural products and miRNAs with ferroptosis-modulating effects were retrieved and organized. Next, a literature search established the connection of a panel of ferroptosis-modulating genes to these ferroptosis-associated natural products. Moreover, ferroptosis-associated miRNAs were inputted into the miRNA database (miRDB) to bioinformatically search the potential targets for the modulation of ferroptosis and exosome biogenesis. Finally, the literature search provided a connection between ferroptosis-modulating miRNAs and natural products. Consequently, the connections from ferroptosis-miRNA-exosome biogenesis to natural product-based anticancer treatments are well-organized. This review sheds light on the research directions for integrating miRNAs and exosome biogenesis into the ferroptosis-modulating therapeutic effects of natural products on cancer and non-cancer diseases.

Protection of Gueichih-Fuling-Wan on cerebral ischemia-induced brain injury in rodents is mediated by trans-cinnamaldehyde via inhibition of neuroinflammation and apoptosis.

Background: Stroke is the leading cause of mortality and morbidity worldwide, and an effective therapeutic strategy for the prevention of patients with cerebral ischemia induced brain injury is lacking. Traditional Chinese medicine with neuroprotective activities might be beneficial and provide alternative therapeutic opportunities for cerebral ischemia. Purposes: This study aimed to evaluate the neuroprotection and possible mechanisms of Gueichih-Fuling-Wan (GFW), its' constitutive herbs, and their active compounds on cerebral ischemia/reperfusion (I/R)-induced brain injury in rodents. Methods: Various doses of extracts (0.25, 0.5, and 1.0 g/kg) of GFW and five constituent herbs (Cinnamomi Cortex, CC; Poria cocos, PC; Paeonia lactifloa, PL; Paeonia suffruticosa, PS and Prunus perisica, PP) were orally administered. Different doses of active compounds (0.5, 1.0, and 2.0 mg/kg) of GFW such as cinnamaldehyde, cinnamic acid (from CC), paeoniflorin (from PL), and paeonol (from PS) were intraperitoneally administered. Their effects on cerebral ischemia/ reperfusion (I/R)induced brain injury in rodents were evaluated. Results: GFW, its' constituent herbs, and the active compounds reduced the infarct area dose-dependently (***P < 0.001). Cinnamaldehyde showed the most significant reduction (***P < 0.001). Therefore, trans-cinnamaldehyde (TCA) was further used to evaluate the neuroprotective mechanism of the I/R-induced brain injury. TCA (10, 20, 30 mg/ kg, p.o.) showed an inhibitory effect of I/R-induced brain damage in mice in a dose-dependent manner. Besides, GFW and TCA dose-dependently reduced the COX-2 protein expression level, and TCA reduced the TUNEL (+) apoptosis. TCA dose-dependently increased the pro-survival NR2A and Bcl-2 protein expression level and decreased the pro-apoptotic NR2B and cytochrome c, caspase 9, and caspase 3 expression (***P < 0.001). Conclusion: The above data revealed that GFW, its' constituent herbs, and active compounds protected against I/R-induced brain injury in rodents. TCA from CC might participate in GFW protecting against cerebral ischemia-induced brain injury by inhibiting neuroinflammation and apoptosis.

Complete genome sequence of a novel totivirus isolated from the leaves of Myrica rubra.

Chinese bayberry is a fruit that is appreciated for its taste. A novel totivirus associated with rolling, disfiguring, chlorotic and vein-clearing symptoms on the leaf apices of Chinese bayberry was identified by transcriptome sequencing and reverse transcription PCR (RT-PCR). The complete genome of the virus was determined to be 4959 nucleotides long, and it contains two open reading frames (ORFs). Its genomic organization is similar to that of previously reported totiviruses. ORF1 encodes a putative coat protein (CP) of 765 aa, and ORF2 encodes an RNA-dependent RNA polymerase (RdRp) of 815 aa. These two putative proteins share 55.1% and 62.6%, amino acid sequence identity, respectively, with the corresponding proteins of Panax notoginseng virus A, respectively. According to the demarcation criteria for totivirus species established by the International Committee on Taxonomy of Viruses (ICTV), the new virus should be considered a member of a new species in the genus totivirus, family Orthototiviridae, which we have tentatively named ''Myrica rubra-associated totivirus'' (MRaTV).

LOXL1-AS1 contributes to metastasis in sonic-hedgehog medulloblastoma by promoting cancer stem-like phenotypes.

BACKGROUND: Medulloblastomas (MBs) are one of the most common malignant brain tumor types in children. MB prognosis, despite improvement in recent years, still depends on clinical and biological risk factors. Metastasis is the leading cause of MB-related deaths, which highlights an unmet need for risk stratification and targeted therapy to improve clinical outcomes. Among the four molecular subgroups, sonic-hedgehog (SHH)-MB harbors clinical and genetic heterogeneity with a subset of high-risk cases. Recently, long non-coding (lnc)RNAs were implied to contribute to cancer malignant progression, but their role in MB remains unclear. This study aimed to identify pro-malignant lncRNAs that have prognostic and therapeutic significance in SHH-MB. METHODS: The Daoy SHH-MB cell line was engineered for ectopic expression of MYCN, a genetic signature of SHH-MB. MYCN-associated lncRNA genes were identified using RNA-sequencing data and were validated in SHH-MB cell lines, MB tissue samples, and patient cohort datasets. SHH-MB cells with genetic manipulation of the candidate lncRNA were evaluated for metastatic phenotypes in vitro, including cell migration, invasion, sphere formation, and expressions of stemness markers. An orthotopic xenograft mouse model was used to evaluate metastasis occurrence and survival. Finally, bioinformatic screening and in vitro assays were performed to explore downstream mechanisms. RESULTS: Elevated lncRNA LOXL1-AS1 expression was identified in MYCN-expressing Daoy cells and MYCN-amplified SHH-MB tumors, and was significantly associated with lower survival in SHH-MB patients. Functionally, LOXL1-AS1 promoted SHH-MB cell migration and cancer stemness in vitro. In mice, MYCN-expressing Daoy cells exhibited a high metastatic rate and adverse effects on survival, both of which were suppressed under LOLX1-AS1 perturbation. Integrative bioinformatic analyses revealed associations of LOXL1-AS1 with processes of cancer stemness, cell differentiation, and the epithelial-mesenchymal transition. LOXL1-AS1 positively regulated the expression of transforming growth factor (TGF)-ß2. Knockdown of TGF-ß2 in SHH-MB cells significantly abrogated their LOXL1-AS1-mediated prometastatic functions. CONCLUSIONS: This study proved the functional significance of LOXL1-AS1 in SHH-MB metastasis by its promotion of TGF-ß2-mediated cancer stem-like phenotypes, providing both prognostic and therapeutic potentials for targeting SHH-MB metastasis.

Protein phosphatase 2A modulation and connection with miRNAs and natural products.

Protein phosphatase 2A (PP2A), a heterotrimeric holoenzyme (scaffolding, catalytic, and regulatory subunits), regulates dephosphorylation for more than half of serine/threonine phosphosites and exhibits diverse cellular functions. Although several studies on natural products and miRNAs have emphasized their impacts on PP2A regulation, their connections lack systemic organization. Moreover, only part of the PP2A family has been investigated. This review focuses on the PP2A-modulating effects of natural products and miRNAs' interactions with potential PP2A targets in cancer and non-cancer cells. PP2A-modulating natural products and miRNAs were retrieved through a literature search. Utilizing the miRDB database, potential PP2A targets of these PP2A-modulating miRNAs for the whole set (17 members) of the PP2A family were retrieved. Finally, PP2A-modulating natural products and miRNAs were linked via a literature search. This review provides systemic directions for assessing natural products and miRNAs relating to the PP2A-modulating functions in cancer and disease treatments.

Performance of ChatGPT on Stage 1 of the Taiwanese medical licensing exam.

Introduction: Since its release by OpenAI in November 2022, numerous studies have subjected ChatGPT to various tests to evaluate its performance in medical exams. The objective of this study is to evaluate ChatGPT's accuracy and logical reasoning across all 10 subjects featured in Stage 1 of Senior Professional and Technical Examinations for Medical Doctors (SPTEMD) in Taiwan, with questions that encompass both Chinese and English. Methods: In this study, we tested ChatGPT-4 to complete SPTEMD Stage 1. The model was presented with multiple-choice questions extracted from three separate tests conducted in February 2022, July 2022, and February 2023. These questions encompass 10 subjects, namely biochemistry and molecular biology, anatomy, embryology and developmental biology, histology, physiology, microbiology and immunology, parasitology, pharmacology, pathology, and public health. Subsequently, we analyzed the model's accuracy for each subject. Result: In all three tests, ChatGPT achieved scores surpassing the 60% passing threshold, resulting in an overall average score of 87.8%. Notably, its best performance was in biochemistry, where it garnered an average score of 93.8%. Conversely, the performance of the generative pre-trained transformer (GPT)-4 assistant on anatomy, parasitology, and embryology was not as good. In addition, its scores were highly variable in embryology and parasitology. Conclusion: ChatGPT has the potential to facilitate not only exam preparation but also improve the accessibility of medical education and support continuous education for medical professionals. In conclusion, this study has demonstrated ChatGPT's potential competence across various subjects within the SPTEMD Stage 1 and suggests that it could be a helpful tool for learning and exam preparation for medical students and professionals.

The clinical application of traditional Chinese medicine NRICM101 in hospitalized patients with COVID-19.

BACKGROUND: The aim of this study was to assess the efficacy and safety of NRICM101 in hospitalized patients with COVID-19. RESEARCH DESIGN AND METHODS: We conducted a retrospective study from 20 April 2021 to 8 July 2021, and evaluated the safety and outcomes (mortality, hospital stay, mechanical ventilation, oxygen support, diarrhea, serum potassium) in COVID-19 patients. Propensity score matching at a 1:2 ratio was performed to reduce confounding factors. RESULTS: A total of 201 patients were analyzed. The experimental group (n = 67) received NRICM101 and standard care, while the control group (n = 134) received standard care alone. No significant differences were observed in mortality (10.4% vs. 14.2%), intubation (13.8% vs. 11%), time to intubation (10 vs. 11 days), mechanical ventilation days (0 vs. 9 days), or oxygen support duration (6 vs. 5 days). However, the experimental group had a shorter length of hospitalization (odds ratio = 0.12, p = 0.043) and fewer mechanical ventilation days (odds ratio = 0.068, p = 0.008) in initially severe cases, along with an increased diarrhea risk (p = 0.035). CONCLUSION: NRICM101 did not reduce in-hospital mortality. However, it shortened the length of hospitalization and reduced mechanical ventilation days in initially severe cases. Further investigation is needed.

Early prediction of distant metastasis in patients with uterine cervical cancer treated with definitive chemoradiotherapy by deep learning using pretreatment [ 18 F]fluorodeoxyglucose positron emission tomography/computed tomography.

OBJECTIVES: A deep learning (DL) model using image data from pretreatment [ 18 F]fluorodeoxyglucose ([ 18 F] FDG)-PET or computed tomography (CT) augmented with a novel imaging augmentation approach was developed for the early prediction of distant metastases in patients with locally advanced uterine cervical cancer. METHODS: This study used baseline [18F]FDG-PET/CT images of newly diagnosed uterine cervical cancer patients. Data from 186 to 25 patients were analyzed for training and validation cohort, respectively. All patients received chemoradiotherapy (CRT) and follow-up. PET and CT images were augmented by using three-dimensional techniques. The proposed model employed DL to predict distant metastases. Receiver operating characteristic (ROC) curve analysis was performed to measure the model's predictive performance. RESULTS: The area under the ROC curves of the training and validation cohorts were 0.818 and 0.830 for predicting distant metastasis, respectively. In the training cohort, the sensitivity, specificity, and accuracy were 80.0%, 78.0%, and 78.5%, whereas, the sensitivity, specificity, and accuracy for distant failure were 73.3%, 75.5%, and 75.2% in the validation cohort, respectively. CONCLUSION: Through the use of baseline [ 18 F]FDG-PET/CT images, the proposed DL model can predict the development of distant metastases for patients with locally advanced uterine cervical cancer treatment by CRT. External validation must be conducted to determine the model's predictive performance.

Puerarin Attenuates Cycloheximide-Induced Oxidative Damage and Memory-Consolidation Impairment in Rats.

BACKGROUND: Cycloheximide (CXM), an antifungal antibiotic, causes impaired memory consolidation as a side effect partially by disturbing the activities of the central catecholaminergic and cholinergic system. Some reports indicated that puerarin prevented memory impairment in various models in rodents. However, the protective effects of puerarin on the side effects of cycloheximide for memory consolidation impairment have not yet been investigated. METHODS: The protective effects of puerarin on CXM-induced memory-consolidation impairment, and memory impairment produced by central administration of AF64A neurotoxin, were investigated using a passive avoidance task in rats. A combination of transmitter receptor agonists and antagonists was used to explore the effects of puerarin on nervous system function. The activity of antioxidant defense systems and neurotransmitter systems in the prefrontal cortex and hippocampus were assayed. RESULTS: Systemic (25 and 50 mg/kg, i.p.) or central (5 and 10 µg/brain, i.c.v.) administration of puerarin attenuated CXM-induced memory-consolidation impairment produced by 1.5 mg/kg CXM (s.c.) in rats. The improvements produced by 50 mg/kg puerarin were blocked by cholinergic antagonists, a 5-HT2 receptor agonist, and an adrenergic receptor antagonist. Puerarin (only at 50 mg/kg, i.p.) reversed the CXM-induced alterations of the levels of norepinephrine in the prefrontal cortex and the levels of monoamines in the hippocampus. Puerarin also increased antioxidant-defense-system activities in the prefrontal cortex and hippocampus, which had been decreased by CXM. CONCLUSIONS: We suggested that the attenuating effects of puerarin on CXM-induced memory-consolidation impairment may be due to decrease oxidative damage and the normalition of the neurotransmitter function in the prefrontal cortex and hippocampus.

Paper-based colorimetric sensor using Photoshop and a smartphone app for the quantitative detection of carbofuran.

We developed a smartphone-assisted microchemistry analyzer for the quantitative detection of carbofuran using a paper-based colorimetric sensor, Photoshop software, and a smartphone app. The changes in color of the carbofuran enzymatic reaction in the paper-based sensor were captured and analyzed using a smartphone-controlled analyzer with an LED light source and a smartphone camera. The high accuracy of this method was demonstrated for the determination of carbofuran with a linear response in the range 0.05-1.0 ppm and limits of detection (LOD) of 0.02 and 0.018 ppm using Photoshop and smartphone app colorimetric analysis, respectively. These two methods not only show the high sensitivity and highly quantitative relationships between the concentrations of commercial carbofuran and characteristic color values of the blue channel in smartphone images but were also applied to infusions of tea. Moreover, the smartphone app is able to GPS tag the location of the test and transmit the results to a website that displays quantitative results from carbofuran samples on a map.

The use of ultrasound for monitoring reduction and ulnar nerve subluxation in pediatric humeral supracondylar fractures.

BACKGROUND: Traditional treatment for displaced humeral supracondylar fractures (SCFs) in children involves closed reduction (CR) under fluoroscopic guidance, percutaneous pinning, and immobilization with a long-arm cast. This study aims to explore the viability of using radiation-free ultrasound (US) for guiding CR and tracking ulnar nerve dynamics during medial pinning, contrasting the US method with the conventional cross pinning technique. MATERIALS AND METHODS: We assessed 70 children with acute displaced SCFs. The US group (n = 30) underwent US-guided reduction, whereas the traditional group (n = 40) underwent fluoroscopy-guided reduction. Both groups received percutaneous cross pinning and subsequent cast immobilization. Postoperative outcomes were compared between the two methods after a 6-month follow-up. In the US group, ultrasonography assessed fracture displacement distances before and after CR. The angle at which the ulnar nerve relocated to the cubital tunnel during elbow extension was documented using real-time US monitoring during medial pinning. RESULTS: The US group demonstrated improved reduction accuracy, increased range of motion, superior restoration of both Baumann and Humeroulnar angles, and a decreased incidence of malunions compared to the traditional group (all p < 0.05). The ultrasonographic measurement of fracture displacement was comparable with that of fluoroscopy (intraclass correlation coefficient > 0.90). In the US group, no ulnar nerve injury was noted, compared to 2.5 % in the traditional group, and real-time US observations revealed ulnar nerve hypermobility, with 53.3 % of patients exhibiting anterior ulnar nerve subluxation at 120° elbow flexion, 40 % at 90°, 16.7 % at 60°, and none at 30° flexion. CONCLUSION: Ultrasound is as reliable as fluoroscopy for evaluating fracture reductions. The use of intra-operative ultrasound significantly improves reduction accuracy and radiographic outcomes while reducing the risk of ulnar nerve injury.

Targeting of RRM2 suppresses DNA damage response and activates apoptosis in atypical teratoid rhabdoid tumor.

BACKGROUND: Atypical teratoid rhabdoid tumors (ATRT) is a rare but aggressive malignancy in the central nervous system, predominantly occurring in early childhood. Despite aggressive treatment, the prognosis of ATRT patients remains poor. RRM2, a subunit of ribonucleotide reductase, has been reported as a biomarker for aggressiveness and poor prognostic conditions in several cancers. However, little is known about the role of RRM2 in ATRT. Uncovering the role of RRM2 in ATRT will further promote the development of feasible strategies and effective drugs to treat ATRT. METHODS: Expression of RRM2 was evaluated by molecular profiling analysis and was confirmed by IHC in both ATRT patients and PDX tissues. Follow-up in vitro studies used shRNA knockdown RRM2 in three different ATRT cells to elucidate the oncogenic role of RRM2. The efficacy of COH29, an RRM2 inhibitor, was assessed in vitro and in vivo. Western blot and RNA-sequencing were used to determine the mechanisms of RRM2 transcriptional activation in ATRT. RESULTS: RRM2 was found to be significantly overexpressed in multiple independent ATRT clinical cohorts through comprehensive bioinformatics and clinical data analysis in this study. The expression level of RRM2 was strongly correlated with poor survival rates in patients. In addition, we employed shRNAs to silence RRM2, which led to significantly decrease in ATRT colony formation, cell proliferation, and migration. In vitro experiments showed that treatment with COH29 resulted in similar but more pronounced inhibitory effect. Therefore, ATRT orthotopic mouse model was utilized to validate this finding, and COH29 treatment showed significant tumor growth suppression and prolong overall survival. Moreover, we provide evidence that COH29 treatment led to genomic instability, suppressed homologous recombinant DNA damage repair, and subsequently induced ATRT cell death through apoptosis in ATRT cells. CONCLUSIONS: Collectively, our study uncovers the oncogenic functions of RRM2 in ATRT cell lines, and highlights the therapeutic potential of targeting RRM2 in ATRT. The promising effect of COH29 on ATRT suggests its potential suitability for clinical trials as a novel therapeutic approach for ATRT.

Machine Learning and Radiomics of Bone Scintigraphy: Their Role in Predicting Recurrence of Localized or Locally Advanced Prostate Cancer.

BACKGROUND: Machine-learning (ML) and radiomics features have been utilized for survival outcome analysis in various cancers. This study aims to investigate the application of ML based on patients' clinical features and radiomics features derived from bone scintigraphy (BS) and to evaluate recurrence-free survival in local or locally advanced prostate cancer (PCa) patients after the initial treatment. METHODS: A total of 354 patients who met the eligibility criteria were analyzed and used to train the model. Clinical information and radiomics features of BS were obtained. Survival-related clinical features and radiomics features were included in the ML model training. Using the pyradiomics software, 128 radiomics features from each BS image's region of interest, validated by experts, were extracted. Four textural matrices were also calculated: GLCM, NGLDM, GLRLM, and GLSZM. Five training models (Logistic Regression, Naive Bayes, Random Forest, Support Vector Classification, and XGBoost) were applied using K-fold cross-validation. Recurrence was defined as either a rise in PSA levels, radiographic progression, or death. To assess the classifier's effectiveness, the ROC curve area and confusion matrix were employed. RESULTS: Of the 354 patients, 101 patients were categorized into the recurrence group with more advanced disease status compared to the non-recurrence group. Key clinical features including tumor stage, radical prostatectomy, initial PSA, Gleason Score primary pattern, and radiotherapy were used for model training. Random Forest (RF) was the best-performing model, with a sensitivity of 0.81, specificity of 0.87, and accuracy of 0.85. The ROC curve analysis showed that predictions from RF outperformed predictions from other ML models with a final AUC of 0.94 and a p-value of <0.001. The other models had accuracy ranges from 0.52 to 0.78 and AUC ranges from 0.67 to 0.84. CONCLUSIONS: The study showed that ML based on clinical features and radiomics features of BS improves the prediction of PCa recurrence after initial treatment. These findings highlight the added value of ML techniques for risk classification in PCa based on clinical features and radiomics features of BS.

Harnessing Nuclear Energy to Gold Nanoparticles for the Concurrent Chemoradiotherapy of Glioblastoma.

Nuclear fission reactions can release massive amounts of energy accompanied by neutrons and γ photons, which create a mixed radiation field and enable a series of reactions in nuclear reactors. This study demonstrates a one-pot/one-step approach to synthesizing radioactive gold nanoparticles (RGNP) without using radioactive precursors and reducing agents. Trivalent gold ions are reduced into gold nanoparticles (8.6-146 nm), and a particular portion of 197Au atoms is simultaneously converted to 198Au atoms, rendering the nanoparticles radioactive. We suggest that harnessing nuclear energy to gold nanoparticles is feasible in the interests of advancing nanotechnology for cancer therapy. A combination of RGNP applied through convection-enhanced delivery (CED) and temozolomide (TMZ) through oral administration demonstrates the synergistic effect in treating glioblastoma-bearing mice. The mean survival for RGNP/TMZ treatment was 68.9 ± 9.7 days compared to that for standalone RGNP (38.4 ± 2.2 days) or TMZ (42.8 ± 2.5 days) therapies. Based on the verification of bioluminescence images, positron emission tomography, and immunohistochemistry inspection, the combination treatment can inhibit the proliferation of glioblastoma, highlighting the niche of concurrent chemoradiotherapy (CCRT) attributed to RGNP and TMZ.

Past-expiration-date liquid disinfectants to deactivate biological and chemical toxins on building material surfaces.

In this study, we evaluated the deactivating efficacy of strong basicity-based (T4-102) and hydrogen peroxide-based (DF-200) disinfectants that were past their expiration date when used to deactivate biological and chemical toxins on building material surfaces. The decontamination efficacies of DF-200 and T4-102 disinfectants against dimethyl methylphosphonate (DMMP) and 2-chloroethyl ethylsulfide (2-CEES) were studied using GC-MS analysis. The bactericidal efficacies of disinfectants against Gram-negative E. coli and P. aeruginosa, and Gram-positive B. subtilis and S. aureus, were assessed in terms of the zone of inhibition, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC). The results indicated that the deactivation efficacy varied significantly according to the disinfectant amount, contact time, and building material. Higher efficacy of up to 99-100% was observed for biological toxins, despite passing their expiration dates. Approximately 70-78% of deactivation efficacies were observed for disinfectants against DMMP on the tile coupon at 100 µL and 24 h contact time. Moreover, the deactivation efficacy of DF-200 was better than that of T4-102. The data presented here demonstrate that the responders may use past-expiration-date disinfectants for efficacious disinfectaion in large-scale contamination incidents.

Peptide immunization against the C-terminal of alpha-synuclein reduces locomotor activity in mice overexpressing alpha-synuclein.

Abnormal accumulation of alpha-synuclein (αSyn) in the remaining nigra dopaminergic neurons is a common neuropathological feature found in patients with Parkinson's disease (PD). Antibody-based immunotherapy has been considered a potential approach for PD treatment. This study aims to investigate the effectiveness of active immunization against αSyn in a mouse model of PD. Adult mice were immunized with or without a synthetic peptide containing the C-terminal residues of human αSyn and activation epitopes, followed by an intranigral injection of adeno-associated virus vectors for overexpressing human αSyn. Upon the peptide injection, αSyn-specific antibodies were raised, accompanied by degeneration of dopaminergic neurons and motor deficits. Furthermore, the induction of neuroinflammation was postulated by the elevation of astroglial and microglial markers in the immunized mice. Instead of lessening αSyn toxicity, this peptide vaccine caused an increase in the pathogenic species of αSyn. Our data demonstrated the potential adverse effects of active immunization to raise antibodies against the C-terminal fragment of αSyn. This drawback highlights the need for further investigation to weigh the pros and cons of immunotherapy in PD. Applying the αSyn C-terminal peptide vaccine for PD treatment should be cautiously exercised. This study provides valuable insights into the intricate interplay among immune intervention, αSyn accumulation, and neurodegeneration.

Imaging prediction of KRAS mutation in patients with rectal cancer through deep metric learning using pretreatment [18F]Fluorodeoxyglucose positron emission tomography/computed tomography.

OBJECTIVES: To predict KRAS mutation in rectal cancer (RC) through computer vision of [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) by using metric learning (ML). METHODS: This study included 160 patients with RC who had undergone preoperative PET/CT. KRAS mutation was identified through polymerase chain reaction analysis. This model combined ML with the deep-learning framework to analyze PET data with or without CT images. The Batch Balance Wrapper framework and K-fold cross-validation were employed during the learning process. A receiver operating characteristic (ROC) curve analysis was performed to assess the model's predictive performance. RESULTS: Genetic alterations in KRAS were identified in 82 (51%) tumors. Both PET and CT images were used, and the proposed model had an area under the ROC curve of 0.836 for its ability to predict a mutation status. The sensitivity, specificity, and accuracy were 75.3%, 79.3%, and 77.5%, respectively. When PET images alone were used, the area under the curve was 0.817, whereas the sensitivity, specificity, and accuracy were 73.2%, 79.6%, and 76.2%, respectively. CONCLUSIONS: The ML model presented herein revealed that baseline 18F-FDG PET/CT images could provide supplemental information to determine KRAS mutation in RC. Additional studies are required to maximize the predictive accuracy. ADVANCES IN KNOWLEDGE: The results of the ML model presented herein indicate that baseline 18F-FDG PET/CT images could provide supplemental information for determining KRAS mutation in RC.The predictive accuracy of the model was 77.5% when both image types were used and 76.2% when PET images alone were used. Additional studies are required to maximize the predictive accuracy.

Extraction of large foreign bodies from the airway by gastrointestinal endoscopy.

Foreign body aspiration is a worldwide health problem that often results in life-threatening complications. Although flexible bronchoscopy is a safe procedure for removal of foreign bodies, it is usually unsuccessful in removing large foreign bodies from the airway. Gastrointestinal (GI) endoscopy, which is frequently used to remove foreign bodies from the gastrointestinal tract, has not been reported for retrieval of airway foreign bodies. In this report, we described three successful cases of removal of large airway foreign bodies by GI endoscopy. To avoid rigid bronchoscopy, GI endoscopy can be considered if flexible bronchoscopy has failed to remove a large or heavy airway foreign body in adult patients.

The Critical Role of Equilibrative Nucleoside Transporter-2 in Modulating Cerebral Damage and Vascular Dysfunction in Mice with Brain Ischemia-Reperfusion.

BACKGROUND: Cerebral vascular protection is critical for stroke treatment. Adenosine modulates vascular flow and exhibits neuroprotective effects, in which brain extracellular concentration of adenosine is dramatically increased during ischemic events and ischemia-reperfusion. Since the equilibrative nucleoside transporter-2 (Ent2) is important in regulating brain adenosine homeostasis, the present study aimed to investigate the role of Ent2 in mice with cerebral ischemia-reperfusion. METHODS: Cerebral ischemia-reperfusion injury was examined in mice with transient middle cerebral artery occlusion (tMCAO) for 90 minutes, followed by 24-hour reperfusion. Infarct volume, brain edema, neuroinflammation, microvascular structure, regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (CMRO2), and the production of reactive oxygen species (ROS) were examined following the reperfusion. RESULTS: Ent2 deletion reduced the infarct volume, brain edema, and neuroinflammation in mice with cerebral ischemia-reperfusion. tMCAO-induced disruption of brain microvessels was ameliorated in Ent2-/- mice, with a reduced expression of matrix metalloproteinases-9 and aquaporin-4 proteins. Following the reperfusion, the rCBF of the wild-type (WT) mice was quickly restored to the baseline, whereas, in Ent2-/- mice, rCBF was slowly recovered initially, but was then higher than that in the WT mice at the later phase of reperfusion. The improved CMRO2 and reduced ROS level support the beneficial effects caused by the changes in the rCBF of Ent2-/- mice. Further studies showed that the protective effects of Ent2 deletion in mice with tMCAO involve adenosine receptor A2AR. CONCLUSIONS: Ent2 plays a critical role in modulating cerebral collateral circulation and ameliorating pathological events of brain ischemia and reperfusion injury.