Tsc2 knockout counteracts ubiquitin-proteasome system insufficiency and delays photoreceptor loss in retinitis pigmentosa.

SignificanceStudies in multiple experimental systems have demonstrated that an increase in proteolytic capacity of post-mitotic cells improves cellular resistance to a variety of stressors, delays cellular aging and senescence. Therefore, approaches to increase the ability of cells to degrade misfolded proteins could potentially be applied to the treatment of a broad spectrum of human disorders. An example would be retinal degenerations, which cause irreversible loss of vision and are linked to impaired protein degradation. This study suggests that chronic activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway in degenerating photoreceptor neurons could stimulate the degradation of ubiquitinated proteins and enhance proteasomal activity through phosphorylation.

Identification of Intersite Distance Effects in Au-Ag Single-Atom Alloy Catalysts Using Single Nanoparticle Collision Electrochemistry.

Regulating the atomic density of single-atom alloys (SAAs) promotes the potential to significantly enhance the electrocatalytic activity. However, conventional methods for study on the electrocatalytic performance of SAAs versus the intersite distance demand exhaustive experiments and characterization. Herein, we present a combinatorial synthesis and analysis method to investigate the intersite distance effect of SAA electrocatalysts. We employ single-nanoparticle collision electrochemistry to realize in situ electrodeposition of a precisely tunable Au atomic density onto individual parent Ag nanoparticles, followed by instantaneous electrocatalytic measurement of the newborn Au-Ag SAAs. In this work, the utility of our method is confirmed by the identification of intersite distance effects of Au-Ag SAAs toward the oxygen reduction reaction. When the site distance between two neighboring Au atoms is 1.9 nm, Au-Ag SAAs exhibit optimal activity. This work provides a simple and efficient method for screening other SAA electrocatalysts with ideal intersite distance at the single-nanoparticle level.

Immunotherapy for Ovarian Cancer: Disappointing or Promising?

Ovarian cancer, one of the deadliest malignancies, lacks effective treatment, despite advancements in surgical techniques and chemotherapy. Thus, new therapeutic approaches are imperative to improving treatment outcomes. Immunotherapy, which has demonstrated considerable success in managing various cancers, has already found its place in clinical practice. This review aims to provide an overview of ovarian tumor immunotherapy, including its basics, key strategies, and clinical research data supporting its potential. In particular, this discussion highlights promising strategies such as checkpoint inhibitors, vaccines, and pericyte transfer, both individually and in combination. However, the advancement of new immunotherapies necessitates large controlled randomized trials, which will undoubtedly shape the future of ovarian cancer treatment.

Assessing shorebird mortalities due to razor clam aquaculture at key migratory stopover sites in southeastern China.

Aquaculture can provide foraging habitat for birds, but it can also result in intentional and accidental mortality. We examined an overlooked conflict between razor clam (Sinonovacula spp.) aquaculture and declining shorebirds in southeastern China's Fujian and Zhejiang provinces. We surveyed 6 out of 11 internationally important stopover sites for these shorebirds and monitored shorebird mortality in 2 sites (Xinghua Bay, Yueqing Bay) with razor clam aquaculture. We visited an additional 32 sites in these 2 provinces to determine if there was netting in other razor clam farms. Approximately 8-9 km2 of intertidal foraging habitat was covered by horizontal nets to prevent birds from feeding on young razor clams at Xinghua Bay and Yueqing Bay. We conservatively estimated that 13,676 (2.5th-97.5th percentile 8,330-21,285) individual shorebirds were entangled in the nets at the 2 monitored sites in April and May 2021, including 2 endangered and 7 near-threatened species. Mortality of 5 species for which we had sufficient data accounted for 0.76% (black-tailed godwit [Limosa limosa]) to 4.27% (terek sandpiper [Xenus cinereus]) of their total flyway populations. This level of mortality could strongly affect their populations. We found netting at 17 additional razor clam farms, indicating a widespread threat to shorebirds. Although razor clams are typically harvested in late March to early April, nets are left on the mudflats throughout the spring and summer, including when the bulk of shorebird migration takes place. Immediately removing these nets after the clam harvest could prevent most of the spring mortality of shorebirds, although this is unlikely to happen without government regulations or economic incentives. To better assess and mitigate the impacts of this conflict, future research should quantify shorebird mortality at other razor clam farms, including during winter, explore less harmful deterrence methods, and assess the socioeconomic factors driving the conflict.

Evaluación de la mortalidad de aves costeras causada por la acuacultura de almejas navaja en sitios importantes de descanso migratorio en el sureste de China Resumen La acuacultura puede proporcionar hábitats de forrajeo para las aves, pero también puede derivar en muertes accidentales o intencionales. Analizamos un conflicto ignorado entre la acuacultura de almeja navaja (Sinonovacula spp.) y la declinación de aves costeras en las provincias de Fujian y Zhejiang del sureste de China. Censamos seis de los once sitios de descanso con importancia internacional para estas aves y monitoreamos su mortalidad en dos sitios en donde se cría la almeja navaja: la bahía de Xinghua y la de Yueqing. Además, visitamos 32 sitios en estas dos provincias para determinar si existían redes en otras granjas de almeja navaja. Unos 8 ­ 9 km2 del hábitat intermareal de forrajeo estaban cubiertos por redes horizontales para evitar que las aves se alimentaran de las almejas juveniles en ambas bahías. Estimamos moderadamente que 13,676 (2.5° ­ 97.5° percentil 8,330 ­ 21,285) individuos de aves costeras se enredaron en las redes en los dos sitios monitoreados durante abril y mayo de 2021, incluyendo a dos especies en peligro y siete casi amenazadas. La mortalidad de las cinco especies para las cuales tuvimos suficientes datos representó del 0.76% (Limosa limosa) al 4.27% (Xenus cinereus) del total de las poblaciones migratorias. Este nivel de mortalidad podría tener un gran efecto sobre las poblaciones de estas especies. Encontramos redes en 17 granjas más, lo que indica una amenaza extendida para las aves costeras. Aunque es típico que se colecte la almeja navaja a finales de marzo y principios de abril, las redes permanecen durante toda la primavera y el verano, incluso cuando ocurre la mayoría de los vuelos migratorios. La eliminación inmediata de estas redes después de la colecta de almejas podría prevenir la mayoría de las muertes primaverales de las aves costeras, aunque no es probable que esto suceda sin regulaciones gubernamentales o incentivos económicos. Para tener mejores evaluaciones y mitigaciones del impacto de este conflicto, una investigación más profunda debería cuantificar la mortalidad de las aves costeras en otras granjas, incluso durante el invierno, explorar métodos de disuasión menos dañinos y evaluar los factores socioeconómicos que causan el conflicto.

Risk Factors for Postpartum Hemorrhage in Severe Pre-Eclampsia: A Retrospective Single-Centre Study of 1953 Cases.

BACKGROUND Severe pre-eclampsia (sPE) and postpartum hemorrhage (PPH) in pregnancy have serious impact on maternal and fetal health and life. Co-occurrence of sPE and PPH often leads to poor pregnancy outcomes. We explored risk factors associated with PPH in women with sPE. MATERIAL AND METHODS This retrospective study included 1953 women with sPE who delivered at the Women's Hospital of Nanjing Medical University between April 2015 and April 2023. Risk factors for developing PPH in sPE were analyzed, and subgroups were analyzed by delivery mode (cesarean and vaginal). RESULTS A total of 197 women with PPH and 1756 women without PPH were included. Binary logistic regression results showed twin pregnancy (P<0.001), placenta accreta spectrum disorders (P=0.045), and placenta previa (P<0.001) were independent risk factors for PPH in women with sPE. Subgroup analysis showed risk factors for PPH in cesarean delivery group were the same as in the total population, but vaginal delivery did not reduce risk of PPH. Spinal anesthesia reduced risk of PPH relative to general anesthesia (P=0.034). Vaginal delivery group had no independent risk factors for PPH; however, magnesium sulfate (P=0.041) reduced PPH incidence. CONCLUSIONS Women with twin pregnancy, placenta accreta spectrum disorders, placenta previa, and assisted reproduction with sPE should be alerted to the risk of PPH, and spinal anesthesia should be preferred in cesarean delivery. Magnesium sulfate should be used aggressively in women with sPE; however, the relationship between magnesium sulfate and PPH risk needs further investigation.

Antimicrobial peptide cecropin B functions in pathogen resistance of Mythimna separata.

Mythimna separata (Lepidoptera: Noctuidae) is an omnivorous pest that poses a great threat to food security. Insect antimicrobial peptides (AMPs) are small peptides that are important effector molecules of innate immunity. Here, we investigated the role of the AMP cecropin B in the growth, development, and immunity of M. separata. The gene encoding M. separata cecropin B (MscecropinB) was cloned. The expression of MscecropinB was determined in different developmental stages and tissues of M. separata. It was highest in the prepupal stage, followed by the pupal stage. Among larval stages, the highest expression was observed in the fourth instar. Tissue expression analysis of fourth instar larvae showed that MscecropinB was highly expressed in the fat body and haemolymph. An increase in population density led to upregulation of MscecropinB expression. MscecropinB expression was also upregulated by the infection of third and fourth instar M. separata with Beauveria bassiana or Bacillus thuringiensis (Bt). RNA interference (RNAi) targeting MscecropinB inhibited the emergence rate and fecundity of M. separata, and resulted in an increased sensitivity to B. bassiana and Bt. The mortality of M. separata larvae was significantly higher in pathogen plus RNAi-treated M. separata than in controls treated with pathogens only. Our findings indicate that MscecropinB functions in the eclosion and fecundity of M. separata and plays an important role in resistance to infection by B. bassiana and Bt.

Pulvinic Acid Derivative Pigments in Lanmaoa asiatica and L. macrocarpa.

Lanmaoa asiatica G. Wu & Zhu L. Yang and L. macrocarpa N. K. Zeng, H. Chai & S. Jiang are two important gourmet bolete in China, and locally named "Jian Shou Qing" meaning their fruiting bodies turn blue after bruising. The genus represents a distinct lineage in Boletaceae. The pigment(s) associated with the discoloration in Lanmaoa has not been identified. The aim of this study was to determine the pigment(s) underpinning the bluing reaction of L. asiatica and L. macrocarpa when bruised. Potential compounds were isolated by HPLC and identified by LC-HRMS and NMR. In total five to six pigments of hydroxylated pulvinic acid derivatives were detected with similar distribution patterns in both L. asiatica and L. macrocarpa, which by abundance were variegatic acid, variegatorubin, xerocomic acid (and/or isoxerocomic acid), xerocomorubin, and atromentic acid. Variegatic acid, the most abundant pigment, was isolated by HPLC, and the structure was further characterized by NMR. The amount of variegatic acid increased after regular cooking, which may suggest its enhanced health benefit as human diet. The types of pigments that cause bluing reactions often differ among families of Boletales. Our results showed that the pigments in Lanmaoa belong to the category of hydroxylated pulvinic acid derivatives, the major bluing compounds in Boletaceae.

Identification and characterization of waterlogging-responsive genes in the parental line of maize hybrid An'nong 876.

Waterlogging stress is an important abiotic stress that adversely affects maize growth and yield. The mechanism regulating the early stage of the maize response to waterlogging stress is largely unknown. In this study, CM37 and cmh15 seedlings were treated with waterlogging stress and then examined in terms of their physiological changes. The results indicated that inbred line cmh15 is more tolerant to waterlogging stress and less susceptible to peroxide-based damages than CM37. The RNA sequencing analysis identified 1,359 down-regulated genes and 830 up-regulated genes in the waterlogging-treated cmh15 plants (relative to the corresponding control levels). According to the Gene Ontology analysis for the differentially expressed genes (DEGs), some important terms were identified which may play important roles in the response to waterlogging stress. Moreover, enriched Kyoto Encyclopedia of Genes and Genomes pathways were also identified for the DEGs. Furthermore, the substantial changes in the expression of 36 key transcription factors may be closely related to the maize in response to waterlogging stress. This study offers important insights into the mechanism in regulating maize tolerance to waterlogging stress, with important foundations for future research.

Extracellular Vesicles Derived from Human Umbilical Cord MSC Improve Vascular Endothelial Function in In Vitro and In Vivo Models of Preeclampsia through Activating Arginine Metabolism.

Endothelial cell damage is an important feature of preeclampsia (PE). Human umbilical mesenchymal stem-cell-derived extracellular vesicles (HUMSCs-derived EVs) have been shown to have therapeutic effects on a variety of diseases and tissue damage. However, the therapeutic effect of HUMSCs-derived EVs on endothelial injury in PE remains unclear. This study explored the possible mechanism of HUMSCs-derived EVs in the treatment of endothelial cell injury. Tumor necrosis factor α- and lipopolysaccharide-induced endothelial dysfunction models were used to evaluate the therapeutic effect of HUMSCs-derived EVs on endothelial injury. We further constructed PE mouse models to explore the function of HUMSCs-derived EVs in vivo. The changes of metabolites in endothelial cells after HUMSCs-derived EVs treatment were analyzed by metabolomics analysis and further validated by cell experiments. HUMSCs-derived EVs treatment can alleviate endothelial cell injury in PE, involving cell proliferation, migration, angiogenesis, and anti-inflammatory. Importantly, administration of HUMSCs-derived EVs improves hypertension and proteinuria in PE mice, alleviates kidney damage, and promotes vascularization in the placenta. Furthermore, metabolomics analysis found that the arginine metabolic pathway is activated after HUMSCs-derived EVs treatment. We also observed increased arginine level, nitric oxide content, and nitric oxide synthase activity, and further experiments proved that activating the arginine metabolic pathway could alleviate endothelial dysfunction. Our results reveal that HUMSCs-derived EVs could ameliorate PE endothelial dysfunction by activating the arginine metabolic pathway and may serve as a therapeutic method for treating PE.

An EMS-induced allele of the brachytic2 gene can reduce plant height in maize.

KEY MESSAGE: D129 is an EMS-induced mutant with dwarf phenotype, which has important breeding potential to cultivate new varieties suitable for high-density planting in maize Plant height is one of the important agronomic traits that affecting maize planting density, identification of superior dwarf mutants can provide important genetic materials for breeding new varieties suitable for high-density planting. In this study, we identified a dwarf mutant, d129, from maize EMS-induced mutant population. Gene mapping indicated that a G-to-A transition in the second exon of the br2 gene was responsible for the dwarf phenotype of the d129 mutant using MutMap method, which was further validated through allelism testing. Compared with WT plants, the average plant height and ear height of d129 were reduced by 26.67% and 39.43%, respectively, mainly due to a decrease in internode length. Furthermore, the d129 mutant exhibited increased internode diameter, which is important for increasing planting density due to the lodging resistance may be enhanced. Endogenous hormone measurement demonstrated that the contents of IAA and GA3 in the internode of the mutant were significantly lower than that of WT plants. RNA-seq analysis indicated that at least fifteen auxin-responsive and signaling-related genes exhibited differential expression, and some genes involved in cell development and other types of hormone signaling pathways, were also identified from the differential expressed genes. These genes may be related to the reduced hormone contents and decreased elongation of internode cells of the d129 mutant. Our study provided a novel dwarf mutant which can be applied in maize breeding to cultivate new varieties suitable for high-density planting.

Absolute phase measurement method based on bidirectional coding patterns.

The stair-phase-coding patterns have been widely used to determine the fringe order for phase unwrapping of the wrapped phase in three-dimensional shape measurement. Although the special coding sequence algorithm can achieve with a large number of codewords, it needs the current codeword and its adjacent codewords to jointly determine the fringe order. If any codeword of the grouped adjacent codewords is incorrectly recognized, it will result in many false fringe orders. It increases the probability of fringe order error in the decoding process. And it is challenging to significantly increase the number of codewords. To solve this problem, we propose an absolute phase measurement method based on bidirectional coding patterns. The wrapped phase of the object is obtained by four-step phase-shifting patterns, and the fringe order is obtained by bidirectional coding patterns. When generating the bidirectional coding patterns, we code two groups of stair phase with different frequencies along the horizontal direction, which respectively represent local fringe order and partition information. Then, we alternately repeat the two groups of stair phase along the vertical direction in the whole pattern to obtain the bidirectional coding patterns. Each local fringe order information and the corresponding partition information in a small region jointly determine the fringe order of pixels in this small region. Fringe order errors in a small region do not affect other regions. To verify the effectiveness of our method, we performed simulations and experiments. Simulation and experimental results show that our method is effective for objects with different sizes and isolated objects.

Surgical Core Excision With Tongue Flap Closure in Combination With Electron Beam Radiotherapy in the Treatment of Ear Keloids.

BACKGROUND: Ear keloids are disfiguring disorders resistant to various treatments. OBJECTIVE: The authors aimed to assess the efficacy of surgical treatment of ear keloids in a Chinese population using a tongue flap with electron beam radiotherapy. METHODS: The authors conducted a retrospective analysis of 41 patients treated at the Affiliated Hospital of Nantong University between January 2018 and May 2021. Core excision with a tongue flap was performed, followed by 3 days of electron beam radiotherapy and 3 to 6 months of pressure clip application. The Vancouver Scar Scale (VSS) and the Visual Analog Scale (VAS) were used to assess the results. RESULTS: The mean age of the patients was 28.10 years (9-61 years). Postoperative follow-up ranged from 5 to 32 months (mean:12.07). The patients underwent 3 days of postoperative radiotherapy followed by pressure clips for 2 to 6 months. Thirty-seven patients had no recurrence, whereas 4 had a mild recurrence (<3 mm in height) with redness and itchiness. The VSS and VASscores significantly decreased. (p < .05). CONCLUSION: Excision with a tongue flap and radiotherapy can be used as the primary treatment for ear keloids considering the good outcome and long-term management.

The Relationship between the Serum NLRP1 Level and Coronary Lesions in Patients with Coronary Artery Disease.

Background: The pathogenesis of coronary artery disease is complex, and inflammation is one of the regulatory factors. The nucleotide-binding oligomerization domain (NOD)-like receptor protein 1 (NLRP1) plays an important role in the cellular inflammatory response, cell apoptosis, cell death, and autoimmune diseases. Whether the level of NLRP1 is related to the severity of coronary artery stenosis in patients with coronary artery disease (CAD) has not been reported. Objective: To test the serum level of NLRP1 in unstable angina (UA) patients and investigate the effect of NLRP1 on coronary stenosis severity of the coronary artery disease (CAD). Methods: 307 patients hospitalized in the Department of Cardiology of the Affiliated Hospital of Xuzhou Medical University for coronary angiography from January 1, 2021, to December 31, 2022 were included. We detect the level of NLRP1 in the serum of the included patients. Patients were divided into UA group and control group according to coronary angiography results and other clinical data. We use logistic regression to screen the influencing factors of UA. Then, subgroups were divided according to the Gensini score and the number of coronary artery lesions, and the difference of serum NLRP1 level between the groups was compared. Spearman correlation analysis was used to explore the correlation between the serum NLRP1 level and Gensini score. We analyze the diagnostic value of NLRP1 for UA by drawing ROC curve. Results: The median level of serum NLRP1 in patients with UA (n = 257) was 49.71 pg/ml, IQR 30.15, 80.21, and that in patients without UA (n = 50) was 24.75 pg/ml, IQR 13.49, 41.95. Serum NLRP1 levels were significantly different among different subgroups. The patient's Gensini score was correlated with the patient's serum NLRP1 level. Conclusion: The serum NLRP1 level is increased in patients with UA, which is increased with the increasing severity of coronary lesions.

Methods for In Vivo Characterization of Proteostasis in the Mouse Retina.

An increasing number of studies connect inherited and age-related retinal degenerations with changes in the regulation of proteostasis. Here, we describe technical aspects of existing assays allowing to assess the status of the ubiquitin-proteasome system (UPS), changes in autophagy, and protein translation in mouse retina in vivo. These methods are helpful for the development and testing approaches to modulate proteostasis and delay vision loss.

Research Hotspots and Trends in the Diagnosis of Chorioamnionitis: Based on Bibliometric Analysis from 2010 to 2022.

OBJECTIVE: This study aimed to conduct a bibliometric analysis of literature related to the diagnosis of chorioamnionitis (CAM) and to point out the current research progress, hotspots, and development trends of CAM research. STUDY DESIGN: Literature on the diagnosis of CAM from the Web of Science Core Collection (WoSCC) between 2010 and 2022 was retrieved. CiteSpace, VOSviewer, and Online Analysis Platform (OALM) were used to draw maps of authors, articles, journals, institutions, countries/regions, and keywords. RESULTS: A total of 312 articles were included, and the number of articles gradually increased over the study period. The author with the largest number of articles was Roberto Romero. The institution with the largest number of articles was Wayne State University School of Medicine, and the United States was the country that produced the largest number of articles. Analysis of keywords and outbreak words suggested that future research hotspots and trends may focus on early treatment of CAM and more precise, noninvasive, and more sensitive diagnoses. CONCLUSION: In this study, visualization software and data information mining were innovatively used to conduct a bibliometric analysis of articles in the field of CAM diagnosis, and the current status, hotspots, and development of this field were obtained. Future research hotspots may be the precision diagnosis and treatment of CAM. KEY POINTS: · There is no bibliometric study on CAM diagnosis in the existing literature.. · The prediction of CAM diagnosis is an important topic to improve maternal and infant prognosis.. · Bibliometrics can effectively guide the direction of future research..

Causal associations of Insomnia and postpartum depression: a two-sample mendelian randomization study.

BACKGROUND: Postpartum depression (PPD), a prevalent social-mental condition, impacts the mother and the newborn and several facets of their lives. It has been suggested that insomnia is related to both the occurrence and progression of PPD. However, because of lingering confounding and bias, it is impossible to determine the cause of this connection using observational analysis. In this study, we evaluate the causal importance of insomnia on postpartum depression using Mendelian randomization (MR). METHODS: Utilizing summary data from genome-wide association studies (GWAS), a two-sample MR study was conducted. A GWAS dataset of IEU study of the United Kingdom Biobank phenotypes comprising 462,341 people of European heritage yielded 38 single-nucleotide polymorphisms (SNPs) for insomnia. The PPD data were provided by the FinnGen project and comprised 7604 cases and 59,601 controls. Inverse variance weighting (IVW) was utilized for the primary MR analysis, with weighted median and MR-Egger as sensitivity analyses. RESULTS: As a result, we found that genetically predicted insomnia was positively associated with postpartum depression. The odds ratios (OR) of PPD were 1.849 (95% (confidence interval) CI 1.011-3.381; p = 0.046). CONCLUSION: For the first time, the causative role of sleeplessness for postpartum depression has been extensively evaluated in the current two-sample MR investigation. Our findings show that insomnia and PPD are related causally.

Recent Advances in Molecularly Imprinted Polymers for Antibiotic Analysis.

The abuse and residues of antibiotics have a great impact on the environment and organisms, and their determination has become very important. Due to their low contents, varieties and complex matrices, effective recognition, separation and enrichment are usually required prior to determination. Molecularly imprinted polymers (MIPs), a kind of highly selective polymer prepared via molecular imprinting technology (MIT), are used widely in the analytical detection of antibiotics, as adsorbents of solid-phase extraction (SPE) and as recognition elements of sensors. Herein, recent advances in MIPs for antibiotic residue analysis are reviewed. Firstly, several new preparation techniques of MIPs for detecting antibiotics are briefly introduced, including surface imprinting, nanoimprinting, living/controlled radical polymerization, and multi-template imprinting, multi-functional monomer imprinting and dummy template imprinting. Secondly, several SPE modes based on MIPs are summarized, namely packed SPE, magnetic SPE, dispersive SPE, matrix solid-phase dispersive extraction, solid-phase microextraction, stir-bar sorptive extraction and pipette-tip SPE. Thirdly, the basic principles of MIP-based sensors and three sensing modes, including electrochemical sensing, optical sensing and mass sensing, are also outlined. Fourthly, the research progress on molecularly imprinted SPEs (MISPEs) and MIP-based electrochemical/optical/mass sensors for the detection of various antibiotic residues in environmental and food samples since 2018 are comprehensively reviewed, including sulfonamides, quinolones, ß-lactams and so on. Finally, the preparation and application prospects of MIPs for detecting antibiotics are outlined.

A critical review on microbial degradation of petroleum-based plastics: quantitatively effects of chemical addition in cultivation media on biodegradation efficiency.

Petroleum-based plastics (PBP) with different properties have been developed to suit various needs of modern lives. Nevertheless, these well-developed properties also present the double-edged sword effect that significantly threatens the sustainability of the environment. This work focuses on the impact of microbial cultivating conditions (the elementary compositions and temperature) to provide insightful information for the process optimization of microbial degradation. The major elementary compositions in cultivation media and temperature from the literature were radically reviewed and assessed using the constructed supervised machine learning algorithm. Fifty-two literatures were collected as a training dataset to investigate the impact of major chemical elements and cultivation temperature upon PBP biodegradation. Among six singular parameters (NH4+, K+, PO43-, Mg2+, Ca2+, and temperature) and thirty corresponding binary parameters, four singular (NH4+, K+, PO43-, and Mg2+) and six binary parameters (NH4+/K+, NH4+/PO43-, NH4+/Ca2+, K+/PO43-, PO43-/Mg2+, Mg2+/Temp) were identified as statistically significant towards microbial degradation through analysis of variance (ANOVA). The binary effect (PO43-/Mg2+) is found to be the most statistically significant towards the microbial degradation of PBP. The concentration range, which locates at 0.1-0.6 g/L for Mg2+ and 0-2.8 g/L for PO43-, was identified to contribute to the maximum PBP biodegradation. Among all the investigated elements, Mg2+ is the only element that is statistically and significantly associated with the variations of cultivation temperature. The optimal preparation conditions within ± 20% uncertainties based upon the range of collected literature reports are recommended. Five representative cultivation elementary compositions (NH4+, K+, PO43-, Mg2+, and Ca2+) and temperature were reviewed from fifty two different literature reports to investigate their impacts on the microbial degradation of PBP using supervised machine learning algorithm. The optimal cultivation conditions based upon collected literature reports to achieve biodegradation over 80% were identified.

Selective Encapsulation of Therapeutic mRNA in Engineered Extracellular Vesicles by DNA Aptamer.

Extracellular vesicles (EV)-based delivery of therapeutic mRNAs is challenged by the low loading efficiency. In this study, we designed a DNA aptamer consisting of two parts: the single strand part recognized the AUG region of target mRNA, preventing mRNA from translation and ribosome assembly; and the double strand part containing the elements recognized by the CD9-ZF (zinc finger) motifs, sorting DNA aptamer-mRNA complex into CD9-ZF engineered EVs. In vitro and in vivo studies revealed that the system could efficiently load functional mRNAs to the EVs. Furthermore, adipose specific delivery of loaded Pgc1α mRNA via the strategy could efficiently induce white adipocyte browning. Similarly, delivery of interleukin-10 (Il-10) mRNA via the strategy had potent anti-inflammatory effect in inflammatory bowel disease (IBD) mouse model. Together, our study has proposed an efficient strategy to load therapeutic mRNAs of interest into EVs, which could be used as a promising strategy for gene therapy.

Simultaneous Determination of Sulfonamides Antibiotics in Environmental Water and Seafood Samples Using Ultrasonic-Assisted Dispersive Liquid-Liquid Microextraction Coupled with High Performance Liquid Chromatography.

The residues and abuse of antibiotics have seriously endangered ecological balance and human health; meanwhile, antibiotics determination is very difficult because of their low levels and multiple categories in complicated matrices. Appropriate sample pretreatment is usually imperative to enrich (ultra)trace antibiotics and eliminate matrix interference prior to chromatographic analysis. Dispersive liquid-liquid microextraction (DLLME) has become an ideal pretreatment technique owing to its simplicity, effectiveness, low-consumption, etc. In this work, an ultrasonic-assisted DLLME (UA-DLLME) was developed for the simultaneous extraction of seven sulfonamides (SAs) antibiotics in environmental water and seafood samples coupled with HPLC-DAD determination. Several parameters affecting UA-DLLME efficiency were systematically optimized, and consequently the SAs were separated and detected within 14.5 min. The obtained limits of detection (LODs) and limits of quantification (LOQs) ranged from 0.7-7.8 µg/L and 2.4-26.0 µg/L for three water samples (seawater, aquaculture wastewater and lake water) and two seafood samples (pomfrets and shrimps). High recoveries (80.0-116.0%) with low relative standard deviations (0.1-8.1%) were achieved for all the tested samples at three spiked levels. Notably, sulfadimethoxine was found at 24.49 µg/L in one seawater sample. The facile, robust and benign DLLME-HPLC method demonstrated promising perspectives for multiresidue analysis of antibiotics.