Pro-CRISPR PcrIIC1-associated Cas9 system for enhanced bacterial immunity.

The CRISPR system is an adaptive immune system found in prokaryotes that defends host cells against the invasion of foreign DNA1. As part of the ongoing struggle between phages and the bacterial immune system, the CRISPR system has evolved into various types, each with distinct functionalities2. Type II Cas9 is the most extensively studied of these systems and has diverse subtypes. It remains uncertain whether members of this family can evolve additional mechanisms to counter viral invasions3,4. Here we identify 2,062 complete Cas9 loci, predict the structures of their associated proteins and reveal three structural growth trajectories for type II-C Cas9. We found that novel associated genes (NAGs) tended to be present within the loci of larger II-C Cas9s. Further investigation revealed that CbCas9 from Chryseobacterium species contains a novel ß-REC2 domain, and forms a heterotetrameric complex with an NAG-encoded CRISPR-Cas-system-promoting (pro-CRISPR) protein of II-C Cas9 (PcrIIC1). The CbCas9-PcrIIC1 complex exhibits enhanced DNA binding and cleavage activity, broader compatibility for protospacer adjacent motif sequences, increased tolerance for mismatches and improved anti-phage immunity, compared with stand-alone CbCas9. Overall, our work sheds light on the diversity and 'growth evolutionary' trajectories of II-C Cas9 proteins at the structural level, and identifies many NAGs-such as PcrIIC1, which serves as a pro-CRISPR factor to enhance CRISPR-mediated immunity.

Chemosensory protein regulates the behavioural response of Frankliniella intonsa and Frankliniella occidentalis to tomato zonate spot virus-Infected pepper (Capsicum annuum).

Many herbivorous insects rely on plant volatiles to locate their host plants. Vector-borne viral infections induce changes in plant volatiles, which render infected plants more attractive to insect vectors. However, the detailed mechanisms underlying the olfactory responses of insect vectors induced by the volatiles produced by virus-infected plants are poorly understood. Here, we show that volatiles emitted by pepper (Capsicum annuum) plants infected with tomato zonate spot virus (TZSV), particularly the volatile cis-3-hexenal, which is recognized by chemosensory protein 1 of the thrips Frankliniella intonsa (FintCSP1), are more attractive to F. intonsa than the volatiles emitted by non-infected pepper plants. FintCSP1 is highly abundant in the antenna of F. intonsa. Silencing of FintCSP1 significantly decreased electroantennogram responses of F. intonsa antennae to cis-3-hexenal and impaired thrips' responses to TZSV-infected pepper plants and cis-3-hexenal, as assessed using a Y-tube olfactometer. Three-dimensional model predictions indicated that FintCSP1 consists of seven α-helixes and two disulfide bridges. Molecular docking analysis suggested that cis-3-hexenal is positioned deep inside the binding pocket of FintCSP1 and binds to residues of the protein. We combined site-directed mutagenesis and fluorescence binding assays and identified three hydrophilic residues, Lys26, Thr28, and Glu67, of FintCSP1 as being critical for cis-3-hexenal binding. Furthermore, CSP of F. occidentalis (FoccCSP) is also a key olfactory protein involved in modulating the behaviour of F. occidentalis to TZSV-infected pepper. This study revealed the specific binding characteristics of CSPs to cis-3-hexenal and confirmed the general hypothesis that virus infections induce changes in host volatiles, which can be recognized by the olfactory proteins of the insect vector to enhance vector attraction and this may facilitate viral spread and transmission.

TIF1gamma controls erythroid cell fate by regulating transcription elongation.

Recent genome-wide studies have demonstrated that pausing of RNA polymerase II (Pol II) occurred on many vertebrate genes. By genetic studies in the zebrafish tif1gamma mutant moonshine we found that loss of function of Pol II-associated factors PAF or DSIF rescued erythroid gene transcription in tif1gamma-deficient animals. Biochemical analysis established physical interactions among TIF1gamma, the blood-specific SCL transcription complex, and the positive elongation factors p-TEFb and FACT. Chromatin immunoprecipitation assays in human CD34(+) cells supported a TIF1gamma-dependent recruitment of positive elongation factors to erythroid genes to promote transcription elongation by counteracting Pol II pausing. Our study establishes a mechanism for regulating tissue cell fate and differentiation through transcription elongation.

Prolonged Exposure to Plant Volatiles does not Significantly Affect Pban Expression and Mating Behavior in Diamondback Moth [Plutella Xylostella (Lepidoptera: Plutellidae)].

Herbivorous insects use plant volatiles to locate hosts, find food, and identify oviposition sites to aid survival and reproduction. Plant volatiles not only regulate the synthesis and release of sex pheromones in insects, but also help them in the search and orientation of sources of sex pheromones. However, after prolonged exposure to plant volatiles, the changes mediating the mating behavior of diamondback moth (DBM) [Plutella xylostella (L.) (Lepidoptera: Plutellidae)] are unclear. DBMs treated with allyl isothiocyanate, a volatile from cruciferous vegetables, did not show improved rates of mating with a limited effect on mating rhythm. This treatment inhibited mating behaviors in 3-day-old DBMs and decreased mating duration in 5-day-old DBMs. After prolonged exposure to allyl isothiocyanate, the total mating duration of DBM was not significantly different from that after prolonged exposure to n-hexane (control). The longest mating duration after emergence in DBM after prolonged exposure to allyl isothiocyanate was delayed by 1 day compared with exposure to n-hexane. Prolonged exposure to plant volatiles intensified the response behavior of DBM to sex pheromones. However, the amount of Z11-16: Ald, a major component of the sex pheromone blend exhibited no change in female pheromone glands. Pheromone biosynthesis activating neuropeptide gene (PBAN) was down-regulated in DBMs after prolonged exposure to plant volatiles. These findings suggest that prolonged exposure (6 h) to plant-derived volatiles have little effect on the mating behavior of DBM. This study provides practical guidance for applying phytochemicals in pest control by regulating insect behavior.

Public Response to Federal Electronic Cigarette Regulations Analyzed Using Social Media Data Through Natural Language Processing: Topic Modeling Study.

BACKGROUND: e-Cigarette (electronic cigarette) use has been a public health issue in the United States. On June 23, 2022, the US Food and Drug Administration (FDA) issued marketing denial orders (MDOs) to Juul Labs Inc for all their products currently marketed in the United States. However, one day later, on June 24, 2022, a federal appeals court granted a temporary reprieve to Juul Labs that allowed it to keep its e-cigarettes on the market. As the conversation around Juul continues to evolve, it is crucial to gain insights into the sentiments and opinions expressed by individuals on social media. OBJECTIVE: This study aims to conduct a comprehensive analysis of tweets before and after the ban on Juul, aiming to shed light on public perceptions and sentiments surrounding this contentious topic and to better understand the life cycle of public health-related policy on social media. METHODS: Natural language processing (NLP) techniques were used, including state-of-the-art BERTopic topic modeling and sentiment analysis. A total of 6023 tweets and 22,288 replies or retweets were collected from Twitter (rebranded as X in 2023) between June 2022 and October 2022. The encoded topics were used in time-trend analysis to depict the boom-and-bust cycle. Content analyses of retweets were also performed to better understand public perceptions and sentiments about this contentious topic. RESULTS: The attention surrounding the FDA's ban on Juul lasted no longer than a week on Twitter. Not only the news (ie, tweets with a YouTube link that directs to the news site) related to the announcement itself, but the surrounding discussions (eg, potential consequences of this ban or block and concerns toward kids or youth health) diminished shortly after June 23, 2022, the date when the ban was officially announced. Although a short rebound was observed on July 4, 2022, which was contributed by the suspension on the following day, discussions dried out in 2 days. Out of the top 50 most retweeted tweets, we observed that, except for neutral (23/45, 51%) sentiment that broadcasted the announcement, posters responded more negatively (19/45, 42%) to the FDA's ban. CONCLUSIONS: We observed a short life cycle for this news announcement, with a preponderance of negative sentiment toward the FDA's ban on Juul. Policy makers could use tactics such as issuing ongoing updates and reminders about the ban, highlighting its impact on public health, and actively engaging with influential social media users who can help maintain the conversation.

A fluorescent terbium-metal-organic framework material for high-sensitivity detection of vomitoxin and oxytetracycline hydrochloride in water.

A unique luminescent lanthanide metal-organic framework (LnMOF)-based fluorescence detection platform was utilized to achieve sensitive detection of vomitoxin (VT) and oxytetracycline hydrochloride (OTC-HCL) without the use of antibodies or biomolecular modifications. The sensor had a fluorescence quenching constant of 9.74 × 106 M-1 and a low detection limit of 0.68 nM for vomitoxin. Notably, this is the first example of a Tb-MOF sensor for fluorescence detection of vomitoxin. We further investigated its response to two mycotoxins, aflatoxin B1 and ochratoxin A, and found that their Stern-Volmer fluorescence quenching constants were lower than those of VT. In addition, the fluorescence sensor realized sensitive detection of OTC-HCL with a detection limit of 0.039 µM. In conclusion, the method has great potential as a sensitive and simple technique to detect VT and OTC-HCL in water.

Development a novel nomogram model for predicting significant hepatic histological changes in chronic hepatitis B virus carriers.

A proportion of chronic hepatitis B virus (HBV) carriers with normal alanine transaminase (ALT) present with significant liver histological changes (SLHC). To construct a noninvasive nomogram model to identify SLHC in chronic HBV carriers with different upper limits of normal (ULNs) for ALT. The training cohort consisted of 732 chronic HBV carriers who were stratified into four sets according to different ULNs for ALT: chronic HBV carriers I, II, III, and IV. The external validation cohort comprised 277 chronic HBV carriers. Logistic regression and least absolute shrinkage and selection operator analyses were applied to develop a nomogram model to predict SLHC. A nomogram model-HBGP (based on hepatitis B surface antigen, gamma-glutamyl transpeptidase, and platelet count) demonstrated good performance in diagnosing SLHC with area under the curve (AUCs) of 0.866 (95% confidence interval [CI]: 0.839-0.892) and 0.885 (95% CI: 0.845-0.925) in the training and validation cohorts, respectively. Furthermore, HBGP displayed high diagnostic values for SLHC with AUCs of 0.866 (95% CI: 0.839-0.892), 0.868 (95% CI: 0.838-0.898), 0.865 (95% CI: 0.828-0.901), and 0.853 (95% CI: 0.798-0.908) in chronic HBV carriers I, II, III, and IV, respectively. Additionally, HBGP showed greater ability in predicting SLHC compared with the existing predictors. HBGP has shown high predictive performance for SLHC, and thus may lead to an informed decision on the initiation of antiviral treatment.

E-cigarette use during pregnancy and its association with adverse birth outcomes in the US.

The popularity of e-cigarette use among young adults is a growing concern. However, little is known about factors associated with e-cigarette use in pregnant women and birth outcomes. In this retrospective cohort study, we evaluated the influence of several factors on behavioral changes in e-cigarette use before and during pregnancy, and assessed the association between e-cigarette use and subsequent birth outcomes among pregnant women. The Population Assessment of Tobacco and Health (PATH) study, a government-sponsored national longitudinal study based in the US, Waves 1 through 4 (2013-2018) were used. Multivariate logistic regressions were conducted to estimate behavioral changes in e-cigarette use during pregnancy and subsequent influence on high-risk birth (e.g., preterm birth, low birth weight, birth defects, etc.) and fetal death. Although pregnant women who quit vaping before pregnancy (OR = 1.14, 95% CI 0.54-2.40) or had any use during pregnancy (OR = 1.19, 95% CI 0.38-3.73) showed non-differential risk of having a high-risk birth in comparison to women who did not initiate vaping, we observed that the usage of mint/menthol flavor was correlated with higher risk of fetus death (OR = 3.27, 95% CI 1.17-9.19). Healthcare providers should encourage e-cigarette users to quit prior to and during early pregnancy.

The Association Between Tobacco Retailer Outlet Density and Prevalence of Cigarette Smoking in Virginia.

OBJECTIVE: We examine the association between tobacco retail outlet density and adult smoking prevalence at the county level in Virginia, controlling for spatial autocorrelations. AIMS AND METHODS: Pooling data from 2020 County Health Rankings (compiled data from various sources including, but not limited to, the National Center for Health Statistics-Mortality Files, the Behavioral Risk Factor Surveillance System (BRFSS), and the American Community Survey) and Counter Tools, we conducted regression analyses that accounted for spatial autocorrelation (spatial lag models, LMlag) and adjusted for county-level access to healthcare, demographics, SES, environmental factors, risk conditions or behaviors, and population health measures. RESULTS: Our estimates provide evidence that every increase of one tobacco retail outlet per 1000 persons was associated with 1.16 percentage points (95% CI: 0.80-1.52) higher smoking prevalence at the county level in Virginia after controlling for spatial autocorrelation. The effect of outlet density was largely explained by social determinants of health such as SES, risky conditions or behaviors, and environmental factors. We further noticed that the impact of social determinants of health were closely related and can be explained by indicators of population health (rates of mental distress (ß = 1.49, 95% CI: 1.31-1.67) and physical inactivity (ß = 0.07, 95% CI: 0.04-0.10). CONCLUSIONS: Although higher tobacco outlet density was associated with an increase in county-level smoking prevalence, the impact of outlet density was largely explained by social determinants of health and mental illness. Improving well-being at the community level could be a promising strategy in future tobacco control policies. IMPLICATION: The influence of tobacco outlet density seems to be explained by other social determinants of health and population level of mental or physical health. Thus, efforts to reduce tobacco use and consequent negative health effects should explore the impact of improving regional living standards. However, a sole focus on economic growth may not be sufficient, whereas a focus on such things as promoting work-life balance and improving overall well-being at the community level may be more.

Social Media Data Mining of Antitobacco Campaign Messages: Machine Learning Analysis of Facebook Posts.

BACKGROUND: Social media platforms provide a valuable source of public health information, as one-third of US adults seek specific health information online. Many antitobacco campaigns have recognized such trends among youth and have shifted their advertising time and effort toward digital platforms. Timely evidence is needed to inform the adaptation of antitobacco campaigns to changing social media platforms. OBJECTIVE: In this study, we conducted a content analysis of major antitobacco campaigns on Facebook using machine learning and natural language processing (NLP) methods, as well as a traditional approach, to investigate the factors that may influence effective antismoking information dissemination and user engagement. METHODS: We collected 3515 posts and 28,125 associated comments from 7 large national and local antitobacco campaigns on Facebook between 2018 and 2021, including the Real Cost, Truth, CDC Tobacco Free (formally known as Tips from Former Smokers, where "CDC" refers to the Centers for Disease Control and Prevention), the Tobacco Prevention Toolkit, Behind the Haze VA, the Campaign for Tobacco-Free Kids, and Smoke Free US campaigns. NLP methods were used for content analysis, including parsimonious rule-based models for sentiment analysis and topic modeling. Logistic regression models were fitted to examine the relationship of antismoking message-framing strategies and viewer responses and engagement. RESULTS: We found that large campaigns from government and nonprofit organizations had more user engagements compared to local and smaller campaigns. Facebook users were more likely to engage in negatively framed campaign posts. Negative posts tended to receive more negative comments (odds ratio [OR] 1.40, 95% CI 1.20-1.65). Positively framed posts generated more negative comments (OR 1.41, 95% CI 1.19-1.66) as well as positive comments (OR 1.29, 95% CI 1.13-1.48). Our content analysis and topic modeling uncovered that the most popular campaign posts tended to be informational (ie, providing new information), where the key phrases included talking about harmful chemicals (n=43, 43%) as well as the risk to pets (n=17, 17%). CONCLUSIONS: Facebook users tend to engage more in antitobacco educational campaigns that are framed negatively. The most popular campaign posts are those providing new information, with key phrases and topics discussing harmful chemicals and risks of secondhand smoke for pets. Educational campaign designers can use such insights to increase the reach of antismoking campaigns and promote behavioral changes.

Sublethal effects of emamectin benzoate on development, reproduction, and vitellogenin and vitellogenin receptor gene expression in Thrips hawaiiensis (Thysanoptera: Thripidae).

Thrips hawaiiensis (Morgan) (Thysanoptera: Thripidae) is a sap-sucking pest that seriously damages several crops and reduces their economic value. Exposure to low concentrations of insecticides may have a sublethal effect on surviving insects. In order to provide a reference for the rational application of emamectin benzoate, its sublethal effects on the development and reproduction of T. hawaiiensis were evaluated. Pupal development time was significantly shorter in T. hawaiiensis treated with sublethal concentrations of emamectin benzoate (LC10 and LC20) than in control. Female adult longevity and female total longevity were significantly longer following LC20 treatment than in the control and LC10 treatment groups. Nevertheless, male adult longevity and male total longevity were significantly shorter in the LC10 treatment group than in the control and LC20 treatment groups. The sublethal concentration of emamectin benzoate (LC20) significantly shortened the preadult stages and the mean generation. Meanwhile, it significantly increased the finite rate of increase, intrinsic rate of increase, and net reproductive rate. The fecundity was significantly higher after LC20 treatment than after LC10 and control treatments. Compared with the control group, the LC10 and LC20 groups of T. hawaiiensis adults showed a significantly higher expression of the vitellogenin (Vg) and vitellogenin receptor (VgR) genes, which played a key role in increasing their fecundity. These findings suggest that short-term exposure to sublethal concentrations of emamectin benzoate may lead to a resurgence and secondary outbreak of T. hawaiiensis infestation. The results have practical applications for the management of this important and noxious pest.

Efficacy and Safety of Theta Burst vs Repetitive Transcranial Magnetic Stimulation for the Treatment of Depression: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Theta burst stimulation (TBS) is more energy- and time-efficient than is standard repetitive transcranial magnetic stimulation (rTMS). However, further studies are needed to analyze TBS therapy for its efficacy and safety compared with standard rTMS in treating depression. The aim of this meta-analysis was to compare TBS therapy with standard rTMS treatment regarding their safety and therapeutic effect on individuals with depression. MATERIALS AND METHODS: Six data bases (Wanfang, the China National Knowledge Infrastructure, PubMed, Embase, Cochrane Library, and PsycINFO) were searched from inception till December 20, 2022. Two independent reviewers selected potentially relevant studies on the basis of the inclusion criteria, extracted data, and evaluated the methodologic quality of the eligible trials using the modified ten-item Physiotherapy Evidence Database scale per Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Finally, ten comparable pairs of nine randomized controlled trials (RCTs) were included for meta-analysis. Summary odds ratios (ORs) of the rates of response, remission, and adverse events were simultaneously calculated using quality-effects (QE) and random-effects (RE) models. Changes in depression scores associated with antidepressant effects were expressed using standardized mean differences simultaneously. This study was registered with the International Prospective Register of Systematic Reviews (CRD42022376790). RESULTS: Nine of the 602 RCTs, covering 1124 patients (616 who had TBS protocols applied vs 508 treated using standard rTMS), were included. Differences in response rates between the above two treatment modalities were not significant (OR = 1.01, 95% CI: 0.88-1.16, p = 0.44, I2 = 0%, RE model; OR = 1.07, 95% CI: 0.87-1.32, p = 0.44, I2 = 0%, QE model). Differences in adverse event rates between TBS and standard rTMS groups were not statistically significant. CONCLUSIONS: TBS has similar efficacy and safety to standard rTMS for treating depression. Considering the short duration of daily stimulation sessions, this meta-analysis supports the continued development of TBS for treating depression.

Mice carrying an analogous heterozygous dynamin 2 K562E mutation that causes neuropathy in humans develop predominant characteristics of a primary myopathy.

Some mutations affecting dynamin 2 (DNM2) can cause dominantly inherited Charcot-Marie-Tooth (CMT) neuropathy. Here, we describe the analysis of mice carrying the DNM2 K562E mutation which has been associated with dominant-intermediate CMT type B (CMTDIB). Contrary to our expectations, heterozygous DNM2 K562E mutant mice did not develop definitive signs of an axonal or demyelinating neuropathy. Rather, we found a primary myopathy-like phenotype in these mice. A likely interpretation of these results is that the lack of a neuropathy in this mouse model has allowed the unmasking of a primary myopathy due to the DNM2 K562E mutation which might be overshadowed by the neuropathy in humans. Consequently, we hypothesize that a primary myopathy may also contribute to the disease mechanism in some CMTDIB patients. We propose that these findings should be considered in the evaluation of patients, the determination of the underlying disease processes and the development of tailored potential treatment strategies.

mTOR controls embryonic and adult myogenesis via mTORC1.

The formation of multi-nucleated muscle fibers from progenitors requires the fine-tuned and coordinated regulation of proliferation, differentiation and fusion, both during development and after injury in the adult. Although some of the key factors that are involved in the different steps are well known, how intracellular signals are coordinated and integrated is largely unknown. Here, we investigated the role of the cell-growth regulator mTOR by eliminating essential components of the mTOR complexes 1 (mTORC1) and 2 (mTORC2) in mouse muscle progenitors. We show that inactivation of mTORC1, but not mTORC2, in developing muscle causes perinatal death. In the adult, mTORC1 deficiency in muscle stem cells greatly impinges on injury-induced muscle regeneration. These phenotypes are because of defects in the proliferation and fusion capacity of the targeted muscle progenitors. However, mTORC1-deficient muscle progenitors partially retain their myogenic function. Hence, our results show that mTORC1 and not mTORC2 is an important regulator of embryonic and adult myogenesis, and they point to alternative pathways that partially compensate for the loss of mTORC1.This article has an associated 'The people behind the papers' interview.

Association between isolated maternal hypothyroxinemia during the first trimester and adverse pregnancy outcomes in Southern Chinese women: a retrospective study of 7051 cases.

BACKGROUND: The association between isolated maternal hypothyroxinemia (IMH) and adverse pregnancy outcomes is still controversial. This study aimed to evaluate the association between IMH during the first trimester and adverse pregnancy outcomes in southern Chinese women. METHODS: This was a hospital-based, retrospective cohort study. The records of 7051 women, including 1337 IMH women and 5714 euthyroid women who had a singleton pregnancy and accepted routine prenatal service at the Third Affiliated Hospital of Sun Yat-Sen University from January 2015 to September 2018, were extracted from the electronic medical records system in this study. Thyroid functions [thyroid-stimulating hormone (TSH), free thyroxine (fT4) and anti-thyroperoxidase autoantibody (TPO-Ab)] had to be measured before 13 weeks and 6 days of gestation. The chi-square test and multivariate logistic regression analysis were applied to evaluate the association between IMH during the first trimester and adverse pregnancy outcomes. RESULTS: Prepregnancy obesity [prepregnancy body mass index (preBMI) ≥ 25 kg/m2] was found to be more common in the IMH group (11.2% vs. 6.1%) (P < 0.05). The prevalence of gestational diabetes mellitus (GDM), postpartum haemorrhage (PPH), macrosomia and large for gestational age (LGA) was higher in the IMH group. However, after using multivariate logistic regression analysis to adjust for confounders (maternal age, educational levels and preBMI), only LGA was shown to be associated with an increased risk in IMH women [adjusted OR: 1.27 (95% CI 1.044-1.566)]. The prevalence of preterm delivery (either < 37 or < 34 weeks), gestational hypertension, preeclampsia, placenta previa, placental abruption, premature rupture of membrane (PROM), intrauterine growth restriction (IUGR), polyhydramnios, stillbirth, small for gestational age (SGA) and low Apgar score did not increase. CONCLUSION: IMH during the first trimester did not increase any risk of adverse pregnancy outcomes in southern Chinese women except LGA.

Prediction of organic pollutant removal using Corynebacterium glutamicum fermentation waste.

The disposal of bio-waste (e.g., Corynebacterium glutamicum) produced by the fermentation industry is a serious problem and has a negative impact on economic returns. Some fermentation waste can be recycled as livestock feed, but much cannot be used. Therefore, other recycling methods must be developed to increase its applications, for example, as an environmentally friendly adsorbent for the removal or recovery of chemicals. To broaden its application as an adsorbent, we carried out comprehensive experimental and theoretical analysis. From the experiments, adsorption affinity values between C. glutamicum and micropollutants were measured, and, based on the experimental values, we developed a predictive model. The experimental results reveal that the degree of adsorption is dependent on the structural properties of the micropollutants. In particular, the adsorbent has remarkable adsorption ability toward cations, whereas anionic and neutral compounds interact weakly with the adsorbent. In addition, we found that adsorption is affected by the sodium chloride concentration. Briefly, an increase in salt concentration increases the adsorption of anions, whereas the opposite behavior is observed for cations. In contrast, the adsorption of neutral compounds was not affected by the presence of salt. The modeling studies revealed that a linear free energy relationship model can be used to predict the adsorption affinity. Based on the developed model, we found that hydrogen-bond basicity, anionic coulombic interactions, and molecular volume are the main contributing factors to the adsorption model. However, to achieve the best predictability (a coefficient of determination (R2) of 0.902), additional parameters, such as the dipolarity/polarizability and dispersive interaction, should be included. This indicates that adsorption is a product of complex interactions.

Optical planar and ridge waveguides formed in Er3+-doped germanate glass by ion implantation and precise diamond blade dicing.

In this work, we report on the preparation and characterization of the planar and ridge optical waveguides in the Er3+-doped germanate glass by combining hydrogen ion implantation and precise diamond blade dicing. The nuclear energy loss and the implantation depth were calculated by the SRIM 2013 software. The refractive index profile was obtained by the reflectivity calculation method. The dark-mode spectrum and the near-field intensity distribution were measured by the prism coupling system and end-face coupling technique, respectively. This work has important reference significance for the development of Er3+-doped germanate glass active devices in the optical communication field.

Rescue of spinal muscular atrophy mouse models with AAV9-Exon-specific U1 snRNA.

Spinal Muscular Atrophy results from loss-of-function mutations in SMN1 but correcting aberrant splicing of SMN2 offers hope of a cure. However, current splice therapy requires repeated infusions and is expensive. We previously rescued SMA mice by promoting the inclusion of a defective exon in SMN2 with germline expression of Exon-Specific U1 snRNAs (ExspeU1). Here we tested viral delivery of SMN2 ExspeU1s encoded by adeno-associated virus AAV9. Strikingly the virus increased SMN2 exon 7 inclusion and SMN protein levels and rescued the phenotype of mild and severe SMA mice. In the severe mouse, the treatment improved the neuromuscular function and increased the life span from 10 to 219 days. ExspeU1 expression persisted for 1 month and was effective at around one five-hundredth of the concentration of the endogenous U1snRNA. RNA-seq analysis revealed our potential drug rescues aberrant SMA expression and splicing profiles, which are mostly related to DNA damage, cell-cycle control and acute phase response. Vastly overexpressing ExspeU1 more than 100-fold above the therapeutic level in human cells did not significantly alter global gene expression or splicing. These results indicate that AAV-mediated delivery of a modified U1snRNP particle may be a novel therapeutic option against SMA.

Healthfulness Assessment of Recipes Shared on Pinterest: Natural Language Processing and Content Analysis.

BACKGROUND: Although Pinterest has become a popular platform for distributing influential information that shapes users' behaviors, the role of recipes pinned on Pinterest in these behaviors is not well understood. OBJECTIVE: This study aims to explore the patterns of food ingredients and the nutritional content of recipes posted on Pinterest and to examine the factors associated with recipes that engage more users. METHODS: Data were collected from Pinterest between June 28 and July 12, 2020 (207 recipes and 2818 comments). All samples were collected via 2 new user accounts with no search history. A codebook was developed with a raw agreement rate of 0.97 across all variables. Content analysis and natural language processing sentiment analysis techniques were employed. RESULTS: Recipes using seafood or vegetables as the main ingredient had, on average, fewer calories and less sodium, sugar, and cholesterol than meat- or poultry-based recipes. For recipes using meat as the main ingredient, more than half of the energy was obtained from fat (277/490, 56.6%). Although the most followed pinners tended to post recipes containing more poultry or seafood and less meat, recipes with higher fat content or providing more calories per serving were more popular, having more shared photos or videos and comments. The natural language processing-based sentiment analysis suggested that Pinterest users weighted taste more heavily than complexity (225/2818, 8.0%) and health (84/2828, 2.9%). CONCLUSIONS: Although popular pinners tended to post recipes with more seafood or poultry or vegetables and less meat, recipes with higher fat and sugar content were more user-engaging, with more photo or video shares and comments. Data on Pinterest behaviors can inform the development and implementation of nutrition health interventions to promote healthy recipe sharing on social media platforms.

CRISPR/Cas9-mediated precise genome modification by a long ssDNA template in zebrafish.

BACKGROUND: Gene targeting by homology-directed repair (HDR) can precisely edit the genome and is a versatile tool for biomedical research. However, the efficiency of HDR-based modification is still low in many model organisms including zebrafish. Recently, long single-stranded DNA (lssDNA) molecules have been developed as efficient alternative donor templates to mediate HDR for the generation of conditional mouse alleles. Here we report a method, zLOST (zebrafish long single-stranded DNA template), which utilises HDR with a long single-stranded DNA template to produce more efficient and precise mutations in zebrafish. RESULTS: The efficiency of knock-ins was assessed by phenotypic rescue at the tyrosinase (tyr) locus and confirmed by sequencing. zLOST was found to be a successful optimised rescue strategy: using zLOST containing a tyr repair site, we restored pigmentation in at least one melanocyte in close to 98% of albino tyr25del/25del embryos, although more than half of the larvae had only a small number of pigmented cells. Sequence analysis showed that there was precise HDR dependent repair of the tyr locus in these rescued pigmented embryos. Furthermore, quantification of zLOST knock-in efficiency at the rps14, nop56 and th loci by next generation sequencing demonstrated that zLOST showed a clear improvement. We utilised the HDR efficiency of zLOST to precisely model specific human disease mutations in zebrafish with ease. Finally, we determined that this method can achieve a germline transmission rate of up to 31.8%. CONCLUSIONS: In summary, these results show that zLOST is a useful method of zebrafish genome editing, particularly for generating desired mutations by targeted DNA knock-in through HDR.