A defective viral genome strategy elicits broad protective immunity against respiratory viruses.

RNA viruses generate defective viral genomes (DVGs) that can interfere with replication of the parental wild-type virus. To examine their therapeutic potential, we created a DVG by deleting the capsid-coding region of poliovirus. Strikingly, intraperitoneal or intranasal administration of this genome, which we termed eTIP1, elicits an antiviral response, inhibits replication, and protects mice from several RNA viruses, including enteroviruses, influenza, and SARS-CoV-2. While eTIP1 replication following intranasal administration is limited to the nasal cavity, its antiviral action extends non-cell-autonomously to the lungs. eTIP1 broad-spectrum antiviral effects are mediated by both local and distal type I interferon responses. Importantly, while a single eTIP1 dose protects animals from SARS-CoV-2 infection, it also stimulates production of SARS-CoV-2 neutralizing antibodies that afford long-lasting protection from SARS-CoV-2 reinfection. Thus, eTIP1 is a safe and effective broad-spectrum antiviral generating short- and long-term protection against SARS-CoV-2 and other respiratory infections in animal models.

Emerging Chemistry for Wide-Temperature Sodium-Ion Batteries.

The shortage of resources such as lithium and cobalt has promoted the development of novel battery systems with low cost, abundance, high performance, and efficient environmental adaptability. Due to the abundance and low cost of sodium, sodium-ion battery chemistry has drawn worldwide attention in energy storage systems. It is widely considered that wide-temperature tolerance sodium-ion batteries (WT-SIBs) can be rapidly developed due to their unique electrochemical and chemical properties. However, WT-SIBs, especially for their electrode materials and electrolyte systems, still face various challenges in harsh-temperature conditions. In this review, we focus on the achievements, failure mechanisms, fundamental chemistry, and scientific challenges of WT-SIBs. The insights of their design principles, current research, and safety issues are presented. Moreover, the possible future research directions on the battery materials for WT-SIBs are deeply discussed. Progress toward a comprehensive understanding of the emerging chemistry for WT-SIBs comprehensively discussed in this review will accelerate the practical applications of wide-temperature tolerance rechargeable batteries.

Arrayed in vivo barcoding for multiplexed sequence verification of plasmid DNA and demultiplexing of pooled libraries.

Sequence verification of plasmid DNA is critical for many cloning and molecular biology workflows. To leverage high-throughput sequencing, several methods have been developed that add a unique DNA barcode to individual samples prior to pooling and sequencing. However, these methods require an individual plasmid extraction and/or in vitro barcoding reaction for each sample processed, limiting throughput and adding cost. Here, we develop an arrayed in vivo plasmid barcoding platform that enables pooled plasmid extraction and library preparation for Oxford Nanopore sequencing. This method has a high accuracy and recovery rate, and greatly increases throughput and reduces cost relative to other plasmid barcoding methods or Sanger sequencing. We use in vivo barcoding to sequence verify >45 000 plasmids and show that the method can be used to transform error-containing dispersed plasmid pools into sequence-perfect arrays or well-balanced pools. In vivo barcoding does not require any specialized equipment beyond a low-overhead Oxford Nanopore sequencer, enabling most labs to flexibly process hundreds to thousands of plasmids in parallel.

NOTCH3 promotes docetaxel resistance of prostate cancer cells through regulating TUBB3 and MAPK signaling pathway.

Docetaxel is the preferred chemotherapeutic agent in patients with castrate-resistant prostate cancer (CRPC). However, patients eventually develop docetaxel resistance and in the absence of effective treatment options. Consequently, it is essential to investigate the mechanisms generating docetaxel resistance and develop novel alternative therapeutic targets. RNA sequencing was undertaken on docetaxel-sensitive and docetaxel-resistant prostate cancer (PCa) cells. Subsequently, chemoresistance, cancer stemness, and lipid metabolism were investigated. To obtain insight into the precise activities and action mechanisms of NOTCH3 in docetaxel-resistant PCa, immunoprecipitation, mass spectrometry, ChIP, luciferase reporter assay, cell metabolism, and animal experiments were performed. Through RNA sequencing analysis, we found that NOTCH3 expression was markedly higher in docetaxel-resistant cells relative to parental cells, and that this trend was continued in docetaxel-resistant PCa tissues. Experiments in vitro and in vivo revealed that NOTCH3 enhanced stemness, lipid metabolism, and docetaxel resistance in PCa. Mechanistically, NOTCH3 is bound to TUBB3 and activates the MAPK signaling pathway. Moreover, NOTCH3 was directly regulated by MEF2A in docetaxel-resistant cells. Notably, targeting NOTCH3 and the MEF2A/TUBB3 signaling axis was related to docetaxel chemoresistance in PCa. Overall, these results demonstrated that NOTCH3 fostered stemness, lipid metabolism, and docetaxel resistance in PCa via the TUBB3 and MAPK signaling pathways. Therefore, NOTCH3 may be employed as a prognostic biomarker in PCa patients. NOTCH3 could be a therapeutic target for PCa patients, particularly those who have developed docetaxel resistance.

The predictive value of peripheral blood CD4 cells ATP concentration for immune-related adverse events in advanced non-small cell lung cancer patients.

OBJECTIVE: Lung cancer with the highest incidence and mortality in the world. Immune checkpoint inhibitors (ICIs), can bring long-term survival benefits to patients, but also can bring immune-related adverse events (irAEs) in some patients during therapy. Therefore, the aim of this study was to investigate the predictive effect of peripheral blood WBC, NLR, sATPCD4 and nATPCD4 on irAEs in advanced non-small cell lung cancer (NSCLC). METHODS: Clinical data of 112 patients with advanced NSCLC who were treated with PD -1/PD -L1 inhibitor in the Fifth Affiliated Hospital of Guangzhou Medical University from December 15, 2019 to April 30, 2023 were retrospectively analyzed. These patients were divided into the irAEs group (n = 27) and non-irAEs group (n = 85). The clinical data of the two groups were compared. Receiver operating characteristic (ROC) curves were drawn to determine the threshold value of baseline peripheral blood parameters to predict the occurrence of irAEs. Multivariate logistic regression analysis was used to explore the relationship between peripheral blood markers and the incidence of irAEs. RESULTS: The patient characteristics have no significant difference between irAEs and non-irAEs group. But the baseline peripheral blood WBC, sATPCD4 and nATPCD4 of patients in the irAEs group were higher than those in the non-irAEs group (p < 0.05), and the NLR in irAEs group was similar to in the non-irAEs group (p = 0.639).Univariate analysis showed that high WBC, sATPCD4 and nATPCD4 may the risk factors for the occurrence of irAEs (p < 0.05). Multivariate logistic regression analysis showed that high sATPCD4 and nATPCD4 were independent risk factors for the occurrence of irAEs (p < 0.05). The best critical values of WBC, sATPCD4 and nATPCD4 before treatment for predicting the occurrence of irAEs were 8.165 × 109cells/L (AUC = 0.705) ,484.5 ng/mL (AUC = 0.777), and 156 ng/mL (AUC = 0.840), respectively. CONCLUSIONS: sATPCD4 and nATPCD4 were independent risk factors for the occurrence of irAEs in advanced NSCLC patients. This discovery provides a new method to predict the occurrence of irAEs in patients. Based on the prediction results, corresponding treatment measures can be taken to reduce the incidence of adverse events.

Streptococcal autolysin promotes dysfunction of swine tracheal epithelium by interacting with vimentin.

Streptococcus suis serotype 2 (SS2) is a major zoonotic pathogen resulting in manifestations as pneumonia and septic shock. The upper respiratory tract is typically thought to be the main colonization and entry site of SS2 in pigs, but the mechanism through which it penetrates the respiratory barrier is still unclear. In this study, a mutant with low invasive potential to swine tracheal epithelial cells (STECs) was screened from the TnYLB-1 transposon insertion mutant library of SS2, and the interrupted gene was identified as autolysin (atl). Compared to wild-type (WT) SS2, Δatl mutant exhibited lower ability to penetrate the tracheal epithelial barrier in a mouse model. Purified Atl also enhanced SS2 translocation across STEC monolayers in Transwell inserts. Furthermore, Atl redistributed the tight junctions (TJs) in STECs through myosin light chain kinase (MLCK) signaling, which led to increased barrier permeability. Using mass spectrometry, co-immunoprecipitation (co-IP), pull-down, bacterial two-hybrid and saturation binding experiments, we showed that Atl binds directly to vimentin. CRISPR/Cas9-targeted deletion of vimentin in STECs (VIM KO STECs) abrogated the capacity of SS2 to translocate across the monolayers, SS2-induced phosphorylation of myosin II regulatory light chain (MLC) and MLCK transcription, indicating that vimentin is indispensable for MLCK activation. Consistently, vimentin null mice were protected from SS2 infection and exhibited reduced tracheal and lung injury. Thus, MLCK-mediated epithelial barrier opening caused by the Atl-vimentin interaction is found to be likely the key mechanism by which SS2 penetrates the tracheal epithelium.

Theoretical Investigation on Dialumenes toward Dihydrogen Activation: Mechanism and Ligand Effect.

Herein, we report a computation study based on the density functional theory calculations to understand the mechanism and ligand effect of the base-stabilized dialumenes toward dihydrogen activation. Among all of the examined modes of dihydrogen activation using the base-stabilized dialumene, we found that the concerted 1,2-hydrogenation of the Al═Al double bond is kinetically more preferable. The concerted 1,2-hydrogenation of the Al═Al double bond adopts an electron-transfer model with certain asynchrony. That is, the initial electron donation from the H-H σ bonding orbital to the empty 3p orbital of the Al1 center is followed by the backdonation from the lone pair electron of the Al2 center to the H-H σ antibonding orbital. Combined with the energy decomposition analysis on the transition states of the concerted 1,2-hydrogenation of the Al═Al double bond and the topographic steric mapping analysis on the free dialumenes, we ascribe the higher reactivity of the aryl-substituted dialumene over the silyl-substituted analogue in dihydrogen activation to the stronger electron-withdrawing effect of the aryl group, which not only increases the flexibility of the Al═Al double bond but also enhances the Lewis acidity of the Al═Al core. Consequently, the aryl-substituted dialumene fragment suffers less geometric deformation, and the orbital interactions between the dialumene and dihydrogen moieties are more attractive during the 1,2-hydrogenation process. Moreover, our calculations also predict that the Al═Al double bond has a good tolerance with the stronger electron-withdrawing group (-CF3) and the weaker σ-donating N-heterocyclic carbene (NHC) analogue (e.g., triazol carbene and NHSi). The reactivity of the dialumene in dihydrogen activation can be further improved by introducing these groups as the supporting ligand and the stabilizing base on the Al═Al core, respectively.

Genomics evolution of Jingmen viruses associated with ticks and vertebrates.

Jingmen virus (JMV) associated with ticks and vertebrates have been found to be related to human disease. We obtained the genome of a Jingmen tick virus (JMTV) strain from Rhipicephalus microplus in Guizhou province and compared the genomes of seven JMV species associated with ticks and vertebrates to understand the evolutionary relationships. The topology of the phylogenetic tree of segment 1 and segment 3 is similar, and segment 2 and segment 4 formed two different topologies, with the main differences being between Alongshan virus (ALSV), Takachi virus, Yanggou tick virus and Pteropus lylei jingmen virus (PLJV), and the possibility of genetic reassortment among these viruses. Moreover, we detected recombination within JMTV and between PLJV and ALSV. The genetic reassortment and recombination that occurs during cross-species transmission of these JMV associated with ticks and vertebrates not only complicates their evolutionary relationships, but also raises the risk of these viruses to humans.

[Changes in mild cognitive impairment and sociodemographic disparity among adults aged 55 years and above in 4 provinces of China].

OBJECTIVE: To investigate the changes in mild cognitive impairment(MCI) and sociodemographic disparity among adults aged 55 years and above in 4 provinces of China. METHODS: A total of 4687 adults aged 55 years and above from Community-based Cohort Study on Nervous System Disease who did not have Alzheimer's disease, participated in both rounds of the survey, and had complete baseline sociodemographic data and two rounds of data on cognitive function were selected. Generalized estimation equations were used to analyse the effect of sociodemographic factors on MCI. RESULTS: The detection rates of MCI in adults aged 55 years and above without Alzheimer's disease in 4 provinces of China in 2018 and 2020 were 48.56% and 42.56% respectively. MCI occurred in 30.11% of those with normal cognition(NC) at baseline, and 44.24% of those with MCI at baseline reverted to NC. The risk of MCI increased and the likelihood of MCI reversion decreased with increasing age and decreasing per capita monthly household income. In the baseline NC population, the risk of MCI in the junior high school and above group was 35% lower than that in the illiterate group(RR=0.65, 95%CI 0.53-0.80), the risk of MCI was lower in those living in rural areas(RR=0.56, 95%CI 0.49-0.65), and the risk of MCI was 1.17 times(95%CI 1.03-1.32) higher in those with a history of chronic diseases than in those without it. In the baseline MCI population, the likelihood of MCI reversion increased with education, the likelihood of MCI reversion was 1.04 times higher for workers than for non-workers(95%CI 1.00-1.08). CONCLUSION: The incidence and reversal rates of MCI were high in adults aged ≥55 years in four provinces of China. Advanced age, low education and low income level are risk factors for cognitive dysfunction.

[Consumption status and growth trends of dairy products among children and adolescents in China from 1991 to 2018].

OBJECTIVE: To explore the dairy consumption among children and adolescents aged 7-17 in China. METHODS: 10 rounds of follow-up data from the "China Health and Nutrition Survey" from 1991 to 2018 were collected, and individuals aged 7-17 were selected as the study subjects. Dietary data was collected by using 3-day 24-hour dietary review method and household weighing accounting method(edible oils and seasonings). Dairy consumption was calculated by converting various dairy products into liquid milk intake using the China Food Composition. After excluding those with missing demographic information, missing data from the "3 days and 24 hours" dietary survey, and abnormal daily energy intake, 18 529 participants were included in the final analysis. Joinpoint regression model was used to analyze the trend of changes in dairy intake. RESULTS: The dairy consumption rate increased from 2.8% in 1991 to 42.3% in 2018, while it increased from 8.4% to 58.8% in urban and from 0.9% to 32.1% in rural areas. Meanwhile, the proportion of people whose dairy intake reaches the recommended intake(300 g/d) increased from 0.2% to 3.0%, and the proportion in rural area was 2.0%, which was lower than that in urban areas(4.9%). From 1991 to 2018, dairy intake increased at a rate of 12.97%(P=0.02), and the growth rate of urban and rural areas were 9.79%(P=0.03) and 15.67%(P<0.01), respectively. There was a faster growth trend from 1991-2004 compared to 2004-2018. The growth rate in urban and rural areas also showed different growth trends. CONCLUSION: The dairy intake of children and adolescents aged 7-17 in China improved significantly from 1991 to 2018, with higher consumption rate in urban areas than in rural areas, but it still need to be improved for health.

[Analysis of food carbon footprint and its socio-demographic disparities in China in 2018].

OBJECTIVE: To analyze food carbon footprint and its socio-demographic disparities among adults in China. METHODS: A total of 12 777 adults aged 18 years and above from the China Health and Nutrition Survey in 2018 who have completed dietary and socio-demographic data were analyzed. The information of food intake were collected by 24 h recalls combined with the weighing of household seasonings. Food consumption was converted into energy intake by the China Food Composition Table. Carbon footprint of 26 food groups were calculated by the food carbon footprint database based on life-cycle assessment(LCA), multinomial logit model was used to analyze the association of socio-demographic factors and food carbon footprint. RESULTS: Average food carbon footprint were decreased with increasing age while increased with increasing income and education levels, and was higher among male than that among female, was higher among urban residents than that among rural residents, was higher in the south than that in the north. Multinomial logit analysis showed that compared with people aged 18-44, the likelihood of occurring high carbon footprint in 60y and above group were 29%(OR=0.71, 95%CI 0.61-0.83) lower than that occurring low carbon footprint. Women were 11%(OR=0.89, 95%CI 0.81-0.99) and 25%(OR=0.75, 95%CI 0.67-0.84) less likely to appear medium and high carbon footprint than low carbon footprint, compared with their male counterparts. In comparison to people living in cities, rural dwellers were 24%(OR=0.76, 95%CI 0.69-0.85) and 38%(OR=0.62, 95%CI 0.55-0.70) less likely to appear medium and high carbon footprint than low carbon footprint. People in the south were 3.89 times(95%CI 3.52-4.30) and 11.35 times(95%CI 10.01-12.88) more likely to occur medium and high carbon footprint than low carbon footprint, compared with people in the north. Participants were more likely to occur medium carbon footprint and high carbon footprint with the increasing income level(OR>1), and were more likely to occur high carbon footprint with the increasing education level(OR>1). CONCLUSION: The food carbon footprint of adults in China in 2018 show different socio-demographic disparities, gender, income and education level are significant factors.

[Change of dietary pattern among young people aged 18-35 in China from 1989 to 2018].

OBJECTIVE: To analyze the dietary patterns changes of young people aged 18-35 in 15 provinces(autonomous regions, municipalities) from 1989 to 2018. METHODS: Using the data of China Health and Nutrition Survey, a total of 25 400 young people aged 18-35 with complete dietary and sociodemographic information from 1989 to 2018 in 15 provinces(autonomous regions, municipalities) were selected as the research objects. Nutrition survey was carried out by using 3 consecutive days of 24-hour review method combined with weighing accounting method. Energy and nutrient intake was calculated based on food composition list. The principal component cluster analysis was used to select food groups and K-mean cluster was uesd to extract dietary patterns. Dwass-Steel-Critchlow-Fligner was used to test the difference of food intake in different dietary patterns. Cochran-Armitage trend test was to analyze the change of dietary patterns with the years. Chi-square test was to analyze the difference of people with different dietary patterns in 2018. RESULTS: The dietary patterns of young people aged 18-35 in 15 provinces(autonomous regions, municipalities) were mainly divided into three categories: "traditional rice", "traditional pasta" and "high-quality protein". In 2018, the proportion of "traditional rice" dietary patterns was higher for men than for women, and the proportion of "high-quality protein" dietary patterns was lower than for women. The proportion of "traditional pasta" dietary pattern in people aged 25-35 was higher than that aged 18-24, and the proportion of "high-quality protein" dietary pattern was lower than that aged 18-24. The proportion of people in urban with "traditional rice" dietary pattern was lower than that in rural areas, and the proportion of "high-quality protein" dietary pattern was higher than that in rural areas. The northern region was dominated by "traditional pasta" dietary pattern, while the southern region was dominated by "traditional rice" dietary pattern, and the proportion of people with "high-quality protein" dietary pattern was higher in the northern region than in the southern region. With the increase of education level and income level, the proportion of people with "high-quality protein" dietary pattern showed an increasing trend. From 1989 to 2018, the "traditional rice" dietary pattern had always maintained a high proportion among young people aged 18-35 in 15 provinces(autonomous regions, municipalities) in China, and the "traditional pasta" dietary pattern had been decreasing since 2009, and the "high-quality protein" dietary pattern had significantly increased since 2011. CONCLUSION: From 1989 to 2018, the proportion of young people aged 18-35 with reasonable dietary pattern has increased in 15 provinces(autonomous regions, municipalities), but the traditional dietary pattern still needs to be improved.

Rates of Mutations and Transcript Errors in the Foodborne Pathogen Salmonella enterica subsp. enterica.

Because errors at the DNA level power pathogen evolution, a systematic understanding of the rate and molecular spectra of mutations could guide the avoidance and treatment of infectious diseases. We thus accumulated tens of thousands of spontaneous mutations in 768 repeatedly bottlenecked lineages of 18 strains from various geographical sites, temporal spread, and genetic backgrounds. Entailing over ∼1.36 million generations, the resultant data yield an average mutation rate of ∼0.0005 per genome per generation, with a significant within-species variation. This is one of the lowest bacterial mutation rates reported, giving direct support for a high genome stability in this pathogen resulting from high DNA-mismatch-repair efficiency and replication-machinery fidelity. Pathogenicity genes do not exhibit an accelerated mutation rate, and thus, elevated mutation rates may not be the major determinant for the diversification of toxin and secretion systems. Intriguingly, a low error rate at the transcript level is not observed, suggesting distinct fidelity of the replication and transcription machinery. This study urges more attention on the most basic evolutionary processes of even the best-known human pathogens and deepens the understanding of their genome evolution.

Pattern Recognition and Visual Detection of Aldehydes Using a Single ESIPT Dye.

The accurate discrimination and quantification of aldehydes is a worthy objective made challenging by their similar chemical reactivities. Considering the nucleophilic reaction mechanism between an aldehyde and a primary amine, it is reasonable to vary the reaction pH to manipulate the reactivity of aldehydes and the stability of the resulting Schiff base for analytical purposes. We have designed and synthesized three benzothiazole-based fluorescent molecules (BS1-BS3) containing an amino group substituted at the ortho-, meta-, and para-positions for aldehyde sensing. It was determined that only BS1 having an amino group at the ortho-position exhibits a significant fluorescence response in the presence of formaldehyde at a particular pH, whereas BS2 and BS3 gave negligible responses, indicating that the ESIPT process in BS1 should be responsible for the changes in its fluorescence. Accordingly, a pH-mediated sensor array BS1SA was constructed by dissolving BS1 in aqueous solvents with different pH values. BS1SA was found to be reliable for the discrimination of seven different aldehydes and identification of unknown aldehyde samples. Moreover, BS1 was successfully applied to prepare a fluorescent test paper for the visual detection of formaldehyde vapor.

Volumetric analysis of effectiveness of embolization for preventing type II endoleaks following endovascular aortic aneurysm repair.

OBJECTIVE: The presence of endoleak was associated with the failure of endovascular aortic aneurysm repair (EVAR) treatment. The key to eliminating type II endoleak has shifted from reintervention to prevention. This study aimed to evaluate the effectiveness and safety of applying fibrin sealant to prevent type II endoleak in conjunction with EVAR. METHODS: All patients with abdominal aortic aneurysm who underwent EVAR from June 2019 to July 2021 were reviewed. Patients were grouped as Group A: standard EVAR with preemptive embolization and Group B: standard EVAR alone. The primary endpoint was the incidence of type II endoleak. The secondary endpoints were aneurysm sac regression, the inferior mesenteric artery patency, the numbers of patent lumbar arteries, and all-cause mortality. RESULTS: A total of 104 patients were included in Group A, and 116 were included in Group B. Technical success rate was 100%. The overall incidence of type II endoleak in Group A was significantly lower than that in Group B (4.8% vs 19.0%). The mean time of freedom from type II endoleak was 22.71 months for Group A (95% confidence interval, 21.59-23.83 months) and 19.89 months for Group B (95% confidence interval, 18.08-21.70 months). The Kaplan-Meier estimate of freedom from type II endoleak showed a significantly longer duration of freedom from type II endoleak in Group A (81.0% vs 95.2%). Group A showed a continuous sac regression tendency. In Group B, the sac volume decreased within 12 months but increased by 3.07 cm3 at 24 months. No complications were noted in both groups. CONCLUSIONS: Nonselective preemptive embolization with porcine fibrin sealant during EVAR was safe and effective in preventing type II endoleak in the short and mid-term. Preemptive embolization can lead to a significantly higher sac regression rate. Larger patient populations and longer follow-ups with randomized control designed trials are expected to verify the long-term effectiveness and safety of preemptive embolization in preventing type II endoleak.

Role of SLC5A2 polymorphisms and effects of genetic polymorphism on sodium glucose cotransporter 2 inhibitorsinhibitor response.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disease characterized by hyperglycaemia. T2DM is a highly heterogeneous polygenic disease. Due to genetic variation, variations in lifestyle and other environmental exposures, there are certain variations in the phenotype of T2DM patients. Sodium glucose cotransporter 2 (SGLT2) inhibitors are novel hypoglycaemic agents that increase urinary glucose excretion by inhibiting glucose reabsorption in the proximal tubules of the kidney. For glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors, studies have confirmed a variety of gene variants that may modify their effects. For SGLT2 inhibitors, research has focused on the SLC5A2 gene encoding SGLT2 and UGT1A9 gene polymorphisms affecting SGLT2 inhibitor metabolism. The SLC5A2 polymorphism rs9934336 have been associated with decreased HbA1c during the oral glucose tolerance test. Common variants of the SLC5A2 gene are related to blood glucose and insulin concentrations, but not glucagon concentrations. SLC5A2 rs9934336 and rs3116150 are related to a lower risk of heart failure. SGLT2 inhibitor exposure of UGT1A9*3 carriers is commonly higher than that of noncarriers, while these effects commonly have no obvious clinical significance on SGLT2 inhibitor pharmacokinetics. In terms of efficacy, general SLC5A2 variants show no significant effect on the response to the SGLT2 inhibitor empagliflozin. At present, research on the relationship between genetic polymorphisms and the efficacy of SGLT2 inhibitors is limited. The main purpose of this review is to elucidate the general effects of SGLT2 polymorphisms and the association between polymorphisms and the treatment response to SGLT2 inhibitors.

ABC-Type, Bola-Form Giant Surfactants: Synthesis and Self-Assembly.

Due to the fast phase separation kinetics and small feature size, the self-assembly of giant molecules has attracted lots of attention. However, there is not much study on multicomponent giant surfactants. In this work, through a modular synthetic strategy, different polyhedral oligomeric silsesquioxane (POSS)-based molecular nanoparticles are installed with diverse functionalities (hydrophobic octavinyl POSS (VPOSS), hydrophilic dihydroxyl-functionalized POSS (DPOSS), and omniphobic perfluoroalkyl-chain-functionalized POSS (FPOSS)) on the ends of one polystyrene (PS) chain to build up a series of triblock bola-form giant surfactants denoted as XPOSS-PSn -FPOSS (X represents V or D). The target molecules are prepared by a combination of atom transfer radical polymerization (ATRP), esterification, as well as Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) and thiol-ene "click" reactions. These macromolecules are thoroughly characterized by combined technologies including nuclear magnetic resonance (NMR), size exclusion chromatography (SEC), and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analyses. It is revealed by small angle X-ray scattering (SAXS) and transmission electron microscopy (TEM) that VPOSS-PSn -FPOSS adopts a two-phase separation scenario where VPOSS and POSS are segregated in one phase. DPOSS-PSn -FPOSS with a third hydrophilic DPOSS shows a three-phase separation scenario, where highly ordered phase structures are difficult to develop owing to the competition of mutual phase separation processes and may be trapped in kinetically metastable states.

Molecular engineering and bioimaging applications of C2-alkenyl indole dyes with tunable emission wavelengths covering visible to NIR light.

As an important member of dyes, small-molecule fluorescent dyes show indispensable value in biomedical fields. Although various molecular dyes have been developed, full-color dyes covering blue to red region derived from a single chromophore are still in urgent demand. In this work, a series of dyes based on C2-alkenyl indole skeleton were synthesized, namely AI dyes, and their photophysical properties, cytotoxicity, and imaging capacity were verified to be satisfactory. Particularly, the maximal emission wavelengths of these dyes could cover a wide range from visible to NIR light with large Stokes shifts. Besides, the optical and structural discrepancies between the C2- and C3- alkenyl AI dyes were discussed in detail, and the theoretical calculations were conducted to provide insights on such structure-activity relationship. Finally, as a proof-of-concept, a fluorescent probe AI-Py-B capable of imaging endogenous ONOO- was presented, demonstrating the bioimaging potentials of these alkenyl indole dyes. This work is anticipated to open up new possibilities for developing dye engineering and bio-applications of natural indole framework.

cncRNAdb: a manually curated resource of experimentally supported RNAs with both protein-coding and noncoding function.

RNA endowed with both protein-coding and noncoding functions is referred to as 'dual-function RNA', 'binary functional RNA (bifunctional RNA)' or 'cncRNA (coding and noncoding RNA)'. Recently, an increasing number of cncRNAs have been identified, including both translated ncRNAs (ncRNAs with coding functions) and untranslated mRNAs (mRNAs with noncoding functions). However, an appropriate database for storing and organizing cncRNAs is still lacking. Here, we developed cncRNAdb, a manually curated database of experimentally supported cncRNAs, which aims to provide a resource for efficient manipulation, browsing and analysis of cncRNAs. The current version of cncRNAdb documents about 2600 manually curated entries of cncRNA functions with experimental evidence, involving more than 2,000 RNAs (including over 1300 translated ncRNAs and over 600 untranslated mRNAs) across over 20 species. In summary, we believe that cncRNAdb will help elucidate the functions and mechanisms of cncRNAs and develop new prediction methods. The database is available at http://www.rna-society.org/cncrnadb/.

Effect of early oral carbohydrate intake after elective Cesarean delivery on maternal body temperature and satisfaction: a randomized controlled trial.

PURPOSE: Although the Enhanced Recovery After Cesarean Delivery (ERAC) consensus statement provides recommendations for early postoperative drinking and eating, evidence from high-quality clinical research directly addressing parturients is sparse. Our objective was to assess if early oral carbohydrate intake after elective Cesarean delivery improves maternal recovery. METHODS: In this randomized controlled trial, we enrolled parturients undergoing elective Cesarean delivery under spinal anesthesia with tympanic membrane temperatures ≤ 36.5 °C immediately upon arrival at the postanesthesia care unit. Parturients were randomized to either 100 mL of oral complex carbohydrate intake (group CC) or 10 mL of water (group C). The primary outcome was maternal tympanic membrane temperature. Other outcomes included maternal thermal comfort score, degree of shivering, satisfaction, degree of thirst and hunger, and gastric emptying assessed by ultrasonography. RESULTS: We included 90 participants in the final analysis. The mean (standard deviation [SD]) maternal body temperature at 120 min after ingestion was 36.7 (0.3) °C in group CC and 36.6 (0.3) °C in group C (difference in means, 0.14 °C; 95% confidence interval, 0.02 to 0.26; P = 0.02). Furthermore, using repeated measure models, the linear trends of temperature changes over time between groups CC and C were significantly different (P = 0.04). The thermal comfort scores at 120 min after ingestion were higher in group CC than in group C (P = 0.02), and the linear trends of shivering score changes over time between groups CC and C also were different (P = 0.003). The mean (SD) visual analogue scale scores for maternal satisfaction were 84 (13) mm in group CC and 47 (20) mm in group C (P < 0.001). Nevertheless, at 90 and 120 min after ingestion, there were no differences between the two groups in the number of participants with a gastric antrum cross-sectional area > 10.3 cm2. CONCLUSIONS: Early oral carbohydrate intake after Cesarean delivery helped to restore maternal body temperature postoperatively and improve maternal satisfaction. Nevertheless, the clinical importance of these finding is unclear, given that most of the differences were small. In addition, there was no delay in maternal gastric emptying after consumption of a complex carbohydrate beverage in the early post-Cesarean period. STUDY REGISTRATION: www.chictr.org.cn (ChiCTR2000031085); first submitted 13 November 2022.

RéSUMé: OBJECTIF: Bien que la déclaration de consensus sur la Récupération améliorée après un accouchement par césarienne (ERAC/RAAC) fournisse des recommandations pour l'ingestion postopératoire précoce de liquides et d'aliments, les données probantes issues de recherches cliniques de haute qualité portant directement sur les personnes parturientes sont rares. Notre objectif était d'évaluer si l'ingestion précoce de glucides par voie orale après une césarienne programmée améliorait la récupération maternelle. MéTHODE: Dans cette étude randomisée contrôlée, nous avons recruté des personnes parturientes bénéficiant d'une césarienne programmée sous rachianesthésie avec une température tympanique ≤ 36,5 °C immédiatement après leur arrivée en salle de réveil. Les personnes parturientes ont été randomisées à recevoir soit 100 mL de glucides complexes par voie orale (groupe GC) ou 10 mL d'eau (groupe C). Le critère d'évaluation principal était la température tympanique maternelle. Les autres critères d'évaluation comprenaient, chez la mère, le score de confort thermique, le degré de frissons, la satisfaction, le degré de soif et de faim, et la vidange gastrique évaluée par échographie. RéSULTATS: Nous avons inclus 90 personnes dans l'analyse finale. La température corporelle maternelle moyenne (écart type [ET]) à 120 minutes après l'ingestion était de 36,7 (0,3) °C dans le groupe GC et de 36,6 (0,3) °C dans le groupe C (différence dans les moyennes, 0,14 °C; intervalle de confiance à 95 %, 0,02 à 0,26; P = 0,02). De plus, à l'aide de modèles à mesures répétées, les tendances linéaires des changements de température au fil du temps entre les groupes GC et C étaient significativement différentes (P = 0,04). Les scores de confort thermique à 120 minutes après l'ingestion étaient plus élevés dans le groupe GC que dans le groupe C (P = 0,02), et les tendances linéaires des changements de score de frissons au fil du temps entre les groupes GC et C étaient également différentes (P = 0,003). Les scores moyens (ET) de l'échelle visuelle analogique concernant la satisfaction maternelle étaient de 84 (13) mm dans le groupe GC et de 47 (20) mm dans le groupe C (P < 0,001). Néanmoins, à 90 et 120 minutes après l'ingestion, il n'y avait aucune différence entre les deux groupes dans le nombre de personnes présentant une section transversale de l'antre gastrique > 10,3 cm2. CONCLUSION: L'ingestion précoce de glucides par voie orale après un accouchement par césarienne a aidé à rétablir la température corporelle maternelle postopératoire et à améliorer la satisfaction maternelle. Néanmoins, l'importance clinique de ces résultats n'est pas claire, étant donné que la plupart des différences étaient faibles. De plus, il n'y avait pas de retard dans la vidange gastrique maternelle après la consommation d'une boisson glucidique complexe au début de la période post-césarienne. ENREGISTREMENT DE L'éTUDE: www.chictr.org.cn (ChiCTR2000031085); soumis pour la première fois le 13 novembre 2022.