Superhydrophobic foam combined with biomass-derived TENG based on upcycled coconut husk for efficient oil-water separation.

The ocean ecological environments are seriously affected by oil spilling and plastic-debris, preventing and significantly reducing marine pollution via using biocomposite production from natural fiber reinforcement is a more friendly way to deal with marine oil pollution. Herein, we upcycled coir-coconut into lignin and coconut shell into spherical TENG by a combination of dip-dry and chemical treatment and used the SiO2 nanoparticles together with cellulose nanofibrils to prepare serial sugar-templated, anisotropic and hybrid foams. The as-prepared lignin/SiO2 porous sponge (LSPS) with a hierarchical porous morphology and uniformly dispersed nanoparticles structure benefits from the advantages of biomass-based additives, which presents reversible large-strain deformation (50%) and high compressive strength (11.42 kpa). Notably, the LSPS was significantly more hydrophobic (WCA ≈150°) than pure silicone-based foams, and its selective absorbability can separate oil from water under continuous pumping. Meanwhile, the coconut husk was also upcycled as a spherical TENG shell by a combination of the nanofiber-enhanced polymer spherical oscillator (CESO), which possessed high triboelectric properties (Uoc = 272 V, Isc = 14.5 µA, Q = 70 nC) and was comparable to the plastic shell TENG at low frequency (1.6 Hz). The monolithic foam structure developed using this clean synthetic strategy holds considerable promise for new applications in sustainable petroleum contamination remediation.

Clinical and metagenomic characteristics of lymphadenopathy related to fever of unknown origin in children.

BACKGROUND: Diagnosis of fever of unknown origin remains challenge for pediatricians. Lymphadenopathy is a separate entity that mainly originates from infection or malignancy. METHODS: 168 patients with FUO accompanied by lymphadenectasis were reviewed. 33 lymph node tissue samples were examined by mNGS. Differences in clinical characteristics were compared among different disease groups. The value of mNGS in diagnosing and improving the clinical situation was assessed. RESULTS: Multivariate analysis revealed that hepatosplenomegaly and LDH levels were associated with infectious diseases. Arthralgia was correlated with non-infectious inflammatory diseases. Weight loss and a node located in supraclavicular region may indicate neoplastic diseases. mNGS-positive rate was 60.60%, higher than that obtained with traditional methods. Treatment for 3/4 patients was adjusted according to the pathogen detected by mNGS, and antibiotics uses was discontinued or degraded in over 1/2 of the patients according to mNGS results. CONCLUSIONS: Clinical characteristics of children with lymphadenopathy related to FUO have limited diagnostic value for distinguishing different kinds of diseases, while mNGS of lymph node tissue serves as a useful tool for identifying infectious diseases, especially those caused by rare pathogens. mNGS results can lead to not only adjustments in targeted treatment but also further confirmation of underlying diseases. IMPACT STATEMENT: 1. The clinical features of children with FUO and lymphadenopathy differ according to disease group,although multivariate analysis indicated little diagnostic value for these features. 2. mNGS on lymph node tissue from children with FUO may serve as a efficient tool for distinguishing infectious diseases from other diseases. This is especially useful when a diagnosis cannot be determined with traditional methods. 3. mNGS targeted treatment can be administered in a timely manner and some underlying diseases can be indicated.

Correction: Immunoassay-aptasensor for the determination of tumor-derived exosomes based on the combination of magnetic nanoparticles and hybridization chain reaction.

[This corrects the article DOI: 10.1039/D0RA10159A.].

Evaluation of the efficiency and drivers of complemented cropland in Southwest China over the past 30 years from the perspective of cropland abandonment.

Complemented croplands are a crucial component of cropland resources and play a significant role in ensuring national food security. In recent decades, to counter the loss of prime farmland caused by urban construction, the Chinese government introduced a requisition-compensation balance policy, leading to the substantial expansion of new croplands. Therefore, there is an urgent need to determine whether these complemented croplands can be effectively used. Taking Southwest China as a case study, we used high-precision long-term land-use data from 1990 to 2020 to reveal the dynamics of complemented cropland utilization, evaluate the efficiency of complemented cropland utilization from the perspective of abandoned farmland, and identify the factors driving complemented cropland use efficiency based on more than 13 million land parcels. The results showed that: (1) From 1990 to 2020, complemented cropland amounted to approximately 1170.07 × 104 hm2, accounting for 32.67% of the total arable land area in 1990. The potential grain production capacity of these complemented croplands was significantly lower than that of base croplands. (2) The abandonment of complemented croplands was more serious than that of base croplands, and 47.03% of the complemented croplands experienced abandonment at least once during the study period, and the average efficiency of the complemented croplands was 75.61%. (3) The labor population ratio, elevation, and land parcel size played pivotal roles in influencing the complemented cropland utilization efficiency; however, there was substantial variation among the different provinces. Labor replacement, overcoming farming difficulties brought by mountainous terrain, and improving farmers' income are the keys to alleviating cropland abandonment in mountainous areas and improving cropland utilization efficiency. This study provides novel insights into the efficiency assessment and exploration of the mechanisms driving complemented croplands and can provide references for cropland management.

Diabetes and two kinds of primary tumors in a patient with thalassemia: a case report and literature review.

Background: Thalassemia is a group of common genetic hematologic disorders characterized by deficient synthesis of the hemoglobin chain. Due to effective blood transfusion and optimization of chelate therapy, the survival of thalassemia patients and their overall quality of life have improved noticeably in the past few decades. As a consequence, the longer life expectancy has led to the manifestation of several concomitant morbidities, including heart disease, infections, cirrhosis, endocrine abnormalities, various malignancies, and so on. In this context, the probability and updated literature about some malignancy cases in patients with thalassemia build new scenarios for the next few years. We describe the first report of a thalassemic patient developing diabetes and head and neck cancer and try to summarize the possible predisposing factors and mechanisms behind their phenomenon. Case presentation: The current case report describes a 50-year-old Asian man who has been diagnosed with thalassemia since childhood. In early 2017, he was also diagnosed with diabetes and started on insulin-hypoglycemic treatment. The patient was then diagnosed with primary non-keratinizing undifferentiated carcinoma of the nasopharynx in late February 2013. A biopsy of the left tongue revealed squamous cell carcinoma (SCC) in late March 2019. Conclusions: We report the first case of a thalassemic patient developing diabetes and squamous cell carcinoma of the head and neck and discuss the possibility of a link between the three diseases. This specific case should alert physicians to the possibility of endocrinopathy and malignancy in thalassemic patients.

Developing a novel framework to re-examine half a century of compound drought and heatwave events in mainland China.

Compound drought and heatwave events (CDHEs) are more devastating than single drought or heatwave events and have gained widespread attention. However, previous studies have not investigated the impacts of the precipitation attenuation effect (PAE) (i.e., the effect of previous precipitation on the dryness and wetness of the current system is attenuated) and event merging (EM) (i.e., merging two CDHEs with short intervals into a single event). Moreover, few studies have assessed short-term CDHEs within monthly scales and their variation characteristics under different background temperatures. Here we propose a novel framework for assessing CDHEs on a daily scale and considering the PAE and EM. We applied this framework to mainland China and investigated the spatiotemporal variation of the CDHE indicators (spatial extent (CDHEspa), frequency (CDHEfre), duration (CHHEdur), and severity (CDHEsev)) from 1968 to 2019. The results suggested that ignoring the PAE and EM led to significant changes in the spatial distribution and magnitude of the CDHE indicators. Daily-scale assessments allowed for monitoring the detailed evolution of CDHEs and facilitated the timely development of mitigation measures. Mainland China experienced frequent CDHEs from 1968 to 2019 (except for the southwestern part of Northwest China (NWC) and the western part of Southwest China (SWC)), whereas, hotspot areas of CDHEdur and CDHEsev had a patchy distribution in different geographical subregions. The CDHE indicators were higher in the warmer 1994-2019 period than in the colder 1968-1993 period, but the rate of increase of the indicators was lower or there was a downward trend. Overall, CDHEs in mainland China have been in a state of remarkable continuous strengthening over the past half a century. This study provides a new quantitative analysis approach for CDHEs.

Fluorescent aptasensor based on the MNPs-CRISPR/Cas12a-TdT for the determination of nasopharyngeal carcinoma-derived exosomes.

A fluorescence aptasensor based on taking the advantage of the combination of magnetic nanoparticles (MNPs), terminal deoxynucleotidyl transferase (TdT), and CRISPR/Cas12a was developed for the determination of nasopharyngeal carcinoma (NPC)-derived exosomes. The MNPs can eliminate background interference due to their magnetic separation capability. TdT can form an ultra-long polynucleotide tail which can bind with multiple crRNA, generating a signal amplification effect. The trans-cleavage activity of CRISPR/Cas12a can be specifically triggered via the crRNA binding with DNA, resulting in the bi-labeled DNA reporter with fluorophore and quencher being cleaved. The excitation wavelength of the fluorescence spectra was 490 nm. Fluorescence spectra with emission wavelengths ranging from 511 to 600 nm were collected. Under the optimization condition, the fabricated fluorescence aptasensor for NPC-derived exosome determination exhibited excellent sensitivity and specificity, with the linear range between 500 to 5 × 104 particles mL-1 and the limit of detection of 100 particles mL-1. It can be used for the determination of NPC-derived exosomes in clinical samples, which has a considerable clinical potential and prospect.

Diagnostic Performance of Metagenomic Next-Generation Sequencing in Pediatric Patients: A Retrospective Study in a Large Children's Medical Center.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) has the potential to become a complementary, if not essential, test in some clinical settings. However, the clinical application of mNGS in a large population of children with various types of infectious diseases (IDs) has not been previously evaluated. METHODS: From April 2019 to April 2021, 640 samples were collected at a single pediatric hospital and classified as ID [479 (74.8%)], non-ID [NID; 156 (24.4%)], and unknown cases [5 (0.8%)], according to the final clinical diagnosis. We compared the diagnostic performance in pathogen detection between mNGS and standard reference tests. RESULTS: According to final clinical diagnosis, the sensitivity and specificity of mNGS were 75.0% (95% CI: 70.8%-79.2%) and 59.0% (95% CI: 51.3%-66.7%), respectively. For distinguishing ID from NID, the sensitivity of mNGS was approximately 45.0% higher than that of standard tests (75.0% vs 30.0%; P < 0.001). For fungal detection, mNGS showed positive results in 93.0% of cases, compared to 43.7% for standard tests (P < 0.001). Diagnostic information was increased in respiratory system samples through the addition of meta-transcriptomic sequencing. Further analysis also showed that the read counts in sequencing data were highly correlated with clinical diagnosis, regardless of whether infection was by single or multiple pathogens (Kendall's tau b = 0.484, P < 0.001). CONCLUSIONS: For pediatric patients in critical condition with suspected infection, mNGS tests can provide valuable diagnostic information to resolve negative or inconclusive routine test results, differentiate ID from NID cases, and facilitate accurate and effective clinical therapeutic decision-making.

Efficacy and Safety for the Use of Half-Dosed Pegylated Granulocyte Colony-Stimulating Factors in Preventing Febrile Neutropenia During Chemotherapy in Patients With Malignant Tumors: A Multicenter, Open-Labeled, Single-Arm Phase 2 Trial.

Background: Prophylactic granulocyte-colony stimulating factor (G-CSF) has been shown to effectively prevent febrile neutropenia (FN) and grade 3/4 neutropenia during myelosuppressive treatment. The present study reports the clinical efficacy and safety of the prophylactic use of G-CSF with a half dose for cancer patients with an intermediate risk of FN combined with ≥1 patient-specific risk during multiple chemotherapy. Methods: This multicenter, one-arm, and open-label clinical study involved 151 patients [median age, 54 years old (range, 46.0-62.5); 38.4% female] with malignant tumors, including >20 different cancers. These patients underwent a total of 604 cycles of chemotherapy and received a half dose of PEG-rhG-CSF administration prior to each cycle. Results: The incidence rate of FN was 3.3% for this cohort during chemotherapy. Chemotherapy delay occurred in 6 (4.0%) patients for 12 (2.0%) cycles. Early termination of cancer treatment occurred in 14 (9.3%) patients. In this cohort, 23 (15.2%) patients required antibiotic use during courses of chemotherapy. A total of 28 (18.5%) patients experienced clear adverse effects during cancer treatment. Conclusion: The prophylactic PEG-rhG-CSF with a half dose can both efficaciously and safely prevent neutropenia for patients of diverse cancers with an intermediate risk of FN combined with ≥1 patient-specific risk during chemotherapy.

Analysis of Human Geography Space Based on Geographic Information System in the Context of Rural Revitalization.

Nowadays, it is proposed "Firmly implement the rural revitalization strategy", and rural revitalization has risen to the level of national-level strategy. Human geography is to respond to the cultural effects produced by various residents with similar living habits together. As a spatial science, GIS, with its unique spatial viewpoint and spatial thinking, reveals the spatial distribution characteristics and dynamic change laws of various things and phenomena from spatial interconnections and interactions. From the spatial objects studied by GIS, this paper puts forward thoughts on the new directions of GIS development: expanding from Earth space to cosmic space, it is necessary to build coordinate system and cosmic geospatial information system, lunar geospatial information system, etc.; extending from outdoor space to indoor space, it is necessary to develop indoor geospatial information system and expand to underwater space and underground space; from macro to micro space, we can develop sports geospatial information system for games, human geospatial information system for life and health management, etc.; facing the era of big data, we can develop theories and methods of spatial analysis of big data and contribute to the development of big data science. Thus, the way of constructing GIS based on human geospatial analysis can be built in the context of the era of rural revitalization. The purpose of the research in this paper is mainly to show the role of GIS in the construction of human geography space. Through GIS means, it can better gather some villages in human geography, have a better form of expression, and can better construct a spatial information system.

Poisoning caused by Coriaria sinica maxim among children in Guizhou Province during 2015 to 2020 / 中国学校卫生

Objective@#To analyze the occurrence and epidemiological characteristics of acute poisoning caused by Coriaria sinica maxdim in Guizhou Province during 2015 to 2020, and to provide scientific basis for prevention of Coriaria sinica maxim poisoning.@*Methods@#A total of 176 cases of Coriaria sinica maxim poisoning were reported in Guizhou Province during 2015 to 2020, with all of the 505 affected were children and adolescents under 16 years old. No death was reported. Poisoning caused by Coriaria sinica maxim was most commonly reported in the year of 2020, with 97 reported incidents and 292 poisonings. Poisoning incidents were most freqently reported in the mature stage of Coriariasinica fruit during April to June, with 153 cases and 437 poisoning cases reported in May. The top three areas reporting Coriaria sinica maxim poisoning included Bijie, Anshun and Zunyi City, with the number of reported eventws being 57, 27, and 27, and poisoned children and adolescents of 160, 90, and 73. Most of the affected children were from rural areas. The median incubation period was 2 hours, and the primary clinical symptoms included vomiting( 93.66 %), nausea(58.02%) and abdominal pain(38.42%).@*Conclusion@#A large number of Coriaria sinica maxim poisoning incidents occur due to unsupervised access to Coriaria sinica maxim among rural children. The publicity and education of children, especially for rural left behind children, should be strengthened to reduce the incidence of Coriaria sinica maxim poisoning.

Poisoning caused by Coriaria sinica maxim among children in Guizhou Province during 2015 to 2020 / 中国学校卫生

Objective@#To analyze the occurrence and epidemiological characteristics of acute poisoning caused by Coriaria sinica maxdim in Guizhou Province during 2015 to 2020, and to provide scientific basis for prevention of Coriaria sinica maxim poisoning.@*Methods@#A total of 176 cases of Coriaria sinica maxim poisoning were reported in Guizhou Province during 2015 to 2020, with all of the 505 affected were children and adolescents under 16 years old. No death was reported. Poisoning caused by Coriaria sinica maxim was most commonly reported in the year of 2020, with 97 reported incidents and 292 poisonings. Poisoning incidents were most freqently reported in the mature stage of Coriariasinica fruit during April to June, with 153 cases and 437 poisoning cases reported in May. The top three areas reporting Coriaria sinica maxim poisoning included Bijie, Anshun and Zunyi City, with the number of reported eventws being 57, 27, and 27, and poisoned children and adolescents of 160, 90, and 73. Most of the affected children were from rural areas. The median incubation period was 2 hours, and the primary clinical symptoms included vomiting( 93.66 %), nausea(58.02%) and abdominal pain(38.42%).@*Conclusion@#A large number of Coriaria sinica maxim poisoning incidents occur due to unsupervised access to Coriaria sinica maxim among rural children. The publicity and education of children, especially for rural left behind children, should be strengthened to reduce the incidence of Coriaria sinica maxim poisoning.

Evaluation of Molecular Point-of-Care Testing for Respiratory Pathogens in Children With Respiratory Infections: A Retrospective Case-Control Study.

Objectives: Overuse of antibiotics and antibiotic resistance are global healthcare problems. In pediatric patients with respiratory infections, viral and bacterial etiologies are challenging to distinguish, leading to irrational antibiotic use. Rapid and accurate molecular diagnostic testing methods for respiratory pathogens has been shown to facilitate effective clinical decision-making and guide antibiotic stewardship interventions in the developed regions, but its impacts on pediatric patient care in the developing countries remain unclear. Methods: In this single-center, retrospective case-control study, we compared demographics, clinical characteristics, especially microbiological findings, and antibiotic usage between pediatric patients with respiratory infection receiving FilmArray Respiratory Panel (FilmArray RP) testing and a matched routine testing control group. Our primary outcome was the duration of intravenous antibiotics treatment (DOT) during hospitalization. Results: Each group consisted of 346 children with a respiratory infection. In the FilmArray RP testing group, the DOT was shorter than that in the routine testing group (6.41 ± 3.67 days versus 7.23 ± 4.27 days; p = 0.006). More patients in the FilmArray RP testing group de-escalated antibiotic treatments within 72 hours of hospitalization (7.80%, 27/346 versus 2.60%, 9/346; p = 0.002). By contrast, fewer patients in the FilmArray RP testing group had escalated antibiotic treatments between 72 hours and seven days (7.80% versus 14.16%; p = 0.007). The cost of hospitalization was significantly lower in the FilmArray RP testing group ($ 1413.51 ± 1438.01 versus $ 1759.37 ± 1929.22; p = 0.008). Notably, the subgroup analyses revealed that the FilmArray RP test could shorten the DOT, improve early de-escalation of intravenous antibiotics within 72 hours of hospitalization, decline the escalation of intravenous antibiotics between 72 hours and seven days, and reduce the cost of hospitalization for both patient populations with or without underlying diseases. Conclusions: Molecular point-of-care testing for respiratory pathogens could help to reduce intravenous antibiotic use and health care costs of pediatric patients with respiratory infections in developing countries.

Immunoassay-aptasensor for the determination of tumor-derived exosomes based on the combination of magnetic nanoparticles and hybridization chain reaction.

The detection of tumor-related exosomes is of great significance. In this work, a fluorescence aptasensor was designed for the determination of tumor-related exosomes based on the capture of magnetic nanoparticles (MNPs) and specific recognition of an aptamer. MNPs were used as substrates to capture the exosomes by modifying the CD63 antibody on the MNP surface. Probe 1 consists of PDL-1 aptamer sequence and a section of other sequences. PDL-1 expression was observed on the surface of exosomes; the aptamer of PDL-1 could combine with PDL-1 with high affinity. Thus, the immunoassay-type compounds of "MNPs-exosomes-probe 1" were formed. The other section of probe 1 triggered the HCR with probe 2 and probe 3 and formed the super-long dsDNA. The addition of GelRed resulted in the generation of an amplified fluorescence signal. The proposed design demonstrated a good linearity with the exosome concentration ranging from 300 to 107 particles per mL and with a low detection limit of 100 particles per mL. This aptasensor also exhibited high specificity for tumor-related exosomes, and was successfully applied in biological samples.

Analysis of plant and poisonous mushroom poisoning events among people aged 0-19 in Guizhou Province from 2015 to 2019 / 中国学校卫生

Objective@#To analyze the epidemiological characteristics of plant and mushroom poisoning events among people aged 0-19 in Guizhou Province from 2015 to 2019, so as to provide the basis for prevention and control of food poisoning events among children and adolescents.@*Methods@#Data of people aged 0 to 19 involved in plant and mushroom poisoning incidents reported by the foodborne disease outbreak surveillance system in Guizhou Province from 2015 to 2019 were collected, verified, sorted and statistically analyzed.@*Results@#From 2015 to 2019, there were 590 cases of plant and mushroom poisoning among people aged 0 to 19 in Guizhou Province, 1 441 people were poisoned and 5 died. In May and September, family and collective dining halls were the places with the highest incidence of plant and poisonous mushroom poisoning incidents, accounting for 90.68% (535/590) of the total incidents. Poisonous mushrooms and masanberry accounted for 71.69% (423/590) of the food poisoning causes, and 5 people died of poisoning were caused by poisonous mushrooms.@*Conclusion@#In the cases of plant and mushroom poisoning among people aged 0-19 years in Guizhou Province,preschool primary and middle school students in rural areas are most vulnerable population of poisoning, so it is necessary to strengthen the publicity and education on the prevention and control of toxic plant and mushroom poisoning among children and teenagers in rural areas, so as to reduce the occurrence of relevant poisoning incidents.

Metformin reverses the drug resistance of cisplatin in irradiated CNE-1 human nasopharyngeal carcinoma cells through PECAM-1 mediated MRPs down-regulation.

Objective: To explore a way to reverse the drug resistance for irradiated CNE-1 human nasopharyngeal carcinoma cells and try to develop a new high efficacy with low toxicity therapeutic approach. Methods: 300 Gy irradiated the CNE-1 human nasopharyngeal carcinoma cells, and then treated with single-agent cisplatin or metformin, or combination of both drugs. MTT assay and FCM were applied to detect cell viability and apoptosis. Western blot and RT-PCR were used to characterize the protein and mRNA expression after various drug administrations. Results: The results presented single-agent metformin was capable of arresting the tumor growth and inducing apoptosis in irradiated CNE-1 cells and also demonstrated a synergy effect with cisplatin. Furthermore, metformin down-regulates the PECAM-1 expression, which could regulate Multi-drug Resistance-associate Proteins (MRPs) expression leading to cisplatin resistance of irradiated CNE-1 cells. A pan-MRP inhibitor, probenecid, can resecure cisplatin resistance leading by radiation. Conclusions: Metformin, due to its independent effects on PECAM-1, had a unique anti-proliferative effect on irradiated CNE-1 cells. It would be a new therapeutic option to conquer cisplatin resistance for advanced NPC patients after radiotherapy.

Impact of viral coinfection and macrolide-resistant mycoplasma infection in children with refractory Mycoplasma pneumoniae pneumonia.

BACKGROUND: Cases of refractory Mycoplasma pneumoniae pneumonia have been increasing recently; however, whether viral coinfection or macrolide-resistant M. infection contribute to the development of refractory M. pneumoniae pneumonia remains unclear. This study aimed to investigate the impacts of viral coinfection and macrolide-resistant M. pneumoniae infection on M. pneumoniae pneumonia in hospitalized children and build a model to predict a severe disease course. METHODS: Nasopharyngeal swabs or sputum specimens were collected from patients with community-acquired pneumonia meeting our protocol who were admitted to Shanghai Children's Medical Center from December 1, 2016, to May 31, 2019. The specimens were tested with the FilmArray Respiratory Panel, a multiplex polymerase chain reaction assay that detects 16 viruses, Bordetella pertussis, M. pneumoniae, and Chlamydophila pneumoniae. Univariate and multivariate logistic regression models were used to identify the risk factors for adenovirus coinfection and macrolide-resistant mycoplasma infection. RESULTS: Among the 107 M. pneumoniae pneumonia patients, the coinfection rate was 56.07%, and 60 (60/107, 56.07%) patients were infected by drug-resistant M. pneumoniae. Adenovirus was the most prevalent coinfecting organism, accounting for 22.43% (24/107). The classification tree confirmed that viral coinfection was more common in patients younger than 3 years old. Adenovirus coinfection and drug-resistant M. pneumoniae infection occurred more commonly in patients with refractory M. pneumoniae pneumonia (P = 0.019; P = 0.001). A prediction model including wheezing, lung consolidation and extrapulmonary complications was used to predict adenovirus coinfection. The area under the receiver operating characteristic curve of the prediction model was 0.795 (95% CI 0.679-0.893, P < 0.001). A prolonged fever duration after the application of macrolides for 48 h was found more commonly in patients infected by drug-resistant M. pneumoniae (P = 0.002). A fever duration longer than 7 days was an independent risk factor for drug-resistant Mycoplasma infection (OR = 3.500, 95% CI = 1.310-9.353, P = 0.012). CONCLUSIONS: The occurrence of refractory M. pneumoniae pneumonia is associated with adenovirus coinfection and infection by drug-resistant M. pneumoniae. A prediction model combining wheezing, extrapulmonary complications and lung consolidation can be used to predict adenovirus coinfection in children with M. pneumoniae pneumonia. A prolonged fever duration indicates drug-resistant M. pneumoniae infection, and a reasonable change in antibiotics is necessary.

CRISPR-Cas12a-Assisted Genome Editing in Amycolatopsis mediterranei.

Amycolatopsis mediterranei U32 is an industrial producer of rifamycin SV, whose derivatives have long been the first-line antimycobacterial drugs. In order to perform genetic modification in this important industrial strain, a lot of efforts have been made in the past decades and a homologous recombination-based method was successfully developed in our laboratory, which, however, requires the employment of an antibiotic resistance gene for positive selection and did not support convenient markerless gene deletion. Here in this study, the clustered regularly interspaced short palindromic repeat (CRISPR) system was employed to establish a genome editing system in A. mediterranei U32. Specifically, the Francisella tularensis subsp. novicida Cas12a (FnCas12a) gene was first integrated into the U32 genome to generate target-specific double-stranded DNA (dsDNA) breaks (DSBs) under the guidance of CRISPR RNAs (crRNAs). Then, the DSBs could be repaired by either the non-homologous DNA end-joining (NHEJ) system or the homology-directed repair (HDR) pathway, generating inaccurate or accurate mutations in target genes, respectively. Besides of A. mediterranei, the present work may also shed light on the development of CRISPR-assisted genome editing systems in other species of the Amycolatopsis genus.

Arylbenzofurans from the Root Bark of Morus alba as Triple Inhibitors of Cholinesterase, ß-Site Amyloid Precursor Protein Cleaving Enzyme 1, and Glycogen Synthase Kinase-3ß: Relevance to Alzheimer's Disease.

Cholinesterase, ß-site amyloid precursor protein cleaving enzyme 1 (BACE1), and glycogen synthase kinase-3ß (GSK-3ß) are the three main enzymes responsible for the early onset of Alzheimer's disease (AD). The main aim of the present study was to delineate and accentuate the triple-inhibitory potential of arylbenzofurans from Morus alba against these enzymes. Overall, the enzyme inhibition assays demonstrated the prominence of mulberrofuran D2 as an inhibitor of AChE, BChE, BACE1, and GSK-3ß enzymes with IC50 values of 4.61, 1.51, 0.73, and 6.36 µM, respectively. Enzyme kinetics revealed different modes of inhibition, and in silico modeling suggested that mulberrofuran D2 inhibited these enzymes with low binding energy through hydrophilic, hydrophobic, and π-cation interactions in the active site cavities. Similarly, in Aß-aggregation assays, mulberrofuran D2 inhibited self-induced and AChE-induced Aß aggregation in a concentration-dependent manner that was superior to reference drugs. These results suggest that arylbenzofurans from M. alba, especially mulberrofuran D2, are triple inhibitors of cholinesterase, BACE1, and GSK-3ß and may represent a novel class of anti-AD drugs.

Anti-Alzheimer's Disease Activity of Bromophenols from a Red Alga, Symphyocladia latiuscula (Harvey) Yamada.

Symphyocladia latiuscula (Harvey) Yamada is a red alga with a myriad of bromophenols accompanied by a diverse array of biological activities. The main purpose of the present study was to characterize the anti-Alzheimer's disease activity of bromophenols from S. latiuscula via inhibition of cholinesterases (AChE and BChE), ß-site amyloid precursor protein cleaving enzyme 1 (BACE1), and glycogen synthase kinase-3ß (GSK-3ß). The results of enzyme inhibition assays demonstrated 2,3,6-tribromo-4,5-dihydroxybenzyl alcohol (1), 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (2), and bis-(2,3,6-tribromo-4,5-dihydroxybenzyl) ether (3) as potent inhibitors of aforementioned enzymes. Among the tested bromophenols, 3 showed multifold higher inhibition of all of the tested enzymes. Enzyme kinetics revealed different modes of inhibition, and in silico molecular docking simulation demonstrated the importance of the 7-OH group and bromine number for H-bond and halogen-bond interactions, respectively. Similarly, 1-3 at 20 µM concentration showed more than 50% inhibition of self-induced Aß25-35 aggregation. These results suggest that bromophenols from S. latiuscula, especially highly brominated (3), may represent a novel class of anti-Alzheimer's disease drugs.