Access to chiral dihydrophenanthridines via a palladium(0)-catalyzed Suzuki coupling and C-H arylation cascade reaction using new chiral-bridged biphenyl bifunctional ligands.

A class of chiral-bridged biphenyl phosphine-carboxylate bifunctional ligands CB-Phos has been developed and successfully applied to Pd(0)-catalyzed single enantioselective C-H arylation and a one pot cascade reaction involving Suzuki cross-coupling and C-H arylation. The catalytic system provides a new and convenient way for the synthesis of versatile chiral dihydrophenanthridines with rich structures and broad functional group tolerance. Good to excellent yields with high enantioselectivities were generally achieved. The reaction mechanism of the cascade reaction was also preliminarily discussed.

Incidence and risk factors of active tuberculosis among older individuals with latent tuberculosis infection: a cohort study in two high-epidemic sites in eastern China.

Background: The influencing factors of the process from latent tuberculosis infection (LTBI) to the onset of active tuberculosis (TB) remain unknown among different population groups, especially among older individuals in high-incidence areas. This study aimed to investigate the development of active TB among older adults with LTBI and identify groups in greatest need of improved prevention and control strategies for TB. Methods: In 2021, we implemented an investigation among older individuals (≥ 65 years old) in two towns in Zhejiang Province with the highest incidence of TB. All participants underwent assessment using standardized questionnaires, physical examinations, interferon-gamma release assays, and chest radiography. All the participants with suspected TB based on the clinical symptoms or abnormal chest radiography results, as well as those with LTBI, were referred for diagnostic investigation in accordance with the national guidelines. Those with an initial diagnosis of TB were then excluded, whereas those with LTBI were included in a follow-up at baseline. Incident patients with active TB were identified from the Chinese Tuberculosis Management Information System, and a multivariate Cox regression model was used to estimate the incidence and risk of TB among those with LTBI. Results: In total, 667 participants with LTBI were followed up for 1,315.3 person-years, revealing a disease density of 1,292.5 individuals/100,000 person-years (17/1,315.3). For those with LTBI, chest radiograph abnormalities had adjusted hazard ratios for active TB of 4.9 (1.6-15.3). Conclusions: The presence of abnormal chest radiography findings increased the risk of active TB among older individuals with LTBI in high-epidemic sites in eastern China.

A conserved molecular logic for neurogenesis to gliogenesis switch in the cerebral cortex.

During development, neural stem cells in the cerebral cortex, also known as radial glial cells (RGCs), generate excitatory neurons, followed by production of cortical macroglia and inhibitory neurons that migrate to the olfactory bulb (OB). Understanding the mechanisms for this lineage switch is fundamental for unraveling how proper numbers of diverse neuronal and glial cell types are controlled. We and others recently showed that Sonic Hedgehog (Shh) signaling promotes the cortical RGC lineage switch to generate cortical oligodendrocytes and OB interneurons. During this process, cortical RGCs generate intermediate progenitor cells that express critical gliogenesis genes Ascl1, Egfr, and Olig2. The increased Ascl1 expression and appearance of Egfr+ and Olig2+ cortical progenitors are concurrent with the switch from excitatory neurogenesis to gliogenesis and OB interneuron neurogenesis in the cortex. While Shh signaling promotes Olig2 expression in the developing spinal cord, the exact mechanism for this transcriptional regulation is not known. Furthermore, the transcriptional regulation of Olig2 and Egfr has not been explored. Here, we show that in cortical progenitor cells, multiple regulatory programs, including Pax6 and Gli3, prevent precocious expression of Olig2, a gene essential for production of cortical oligodendrocytes and astrocytes. We identify multiple enhancers that control Olig2 expression in cortical progenitors and show that the mechanisms for regulating Olig2 expression are conserved between the mouse and human. Our study reveals evolutionarily conserved regulatory logic controlling the lineage switch of cortical neural stem cells.

Carbon-based molecular properties efficiently predicted by deep learning-based quantum chemical simulation with large language models.

The prediction of thermodynamic properties of carbon-based molecules based on their geometrical conformation using fluctuation and density functional theories has achieved great success in the field of energy chemistry, while the excessive computational cost provides both opportunities and challenges for the integration of machine learning. In this work, a deep learning-based quantum chemical prediction model was constructed for efficient prediction of thermodynamic properties of carbon-based molecules. We constructed a novel framework - encoding the 3D information into a large language model (LLM), which in turn generates a 2D SMILES string, while embedding a learnable encoding designed to preserve the integrity of the original 3D information, providing better structural information for the model. Additionally, we have designed an equivariant learning module to encompass representations of conformations and feature learning for conformational sampling. This framework aims to predict thermodynamic properties more accurately than learning from 2D topology alone, while providing faster computational speeds than conventional simulations. By combining machine learning and quantum chemistry, we pioneer efficient practical applications in the field of energy chemistry. Our model advances the integration of data-driven and physics-based modeling to unlock novel insights into carbon-based molecules.

Abnormal coagulation after hepatectomy in patients with normal preoperative coagulation function.

BACKGROUND: To explore the risk factors for postoperative abnormal coagulation (PAC) and establish a predictive model for patients with normal preoperative coagulation function who underwent hepatectomy. MATERIALS AND METHODS: A total of 661 patients with normal preoperative coagulation function who underwent hepatectomy between January 2015 and December 2021 at the First Affiliated Hospital of Sun Yat-sen University were divided into two groups: the postoperative abnormal coagulation group (PAC group, n = 362) and the normal coagulation group (non-PAC group, n = 299). Univariate and multivariate logistic analyses were used to identify the risk factors for PAC. RESULTS: The incidence of PAC in 661 patients who underwent hepatectomy was 54.8% (362/661). The least absolute shrinkage and selection operator (LASSO) method was used for multivariate logistic regression analysis. The preoperative international normalized ratio (INR), intraoperative succinyl gelatin infusion and major hepatectomy were found to be independent risk factors for PAC. A nomogram for predicting the PAC after hepatectomy was constructed. The model presented a receiver operating characteristic (ROC) curve of 0.742 (95% confidence interval (CI): 0.697-0.786) in the training cohort. The validation set demonstrated a promising ROC of 0.711 (95% CI: 0.639-0.783), and the calibration curve closely approximated the true incidence. Decision curve analysis (DCA) was performed to assess the clinical usefulness of the predictive model. The risk of PAC increased when the preoperative international normalized ratio (INR) was greater than 1.025 and the volume of intraoperative succinyl gelatin infusion was greater than 1500 ml. CONCLUSION: The PAC is closely related to the preoperative INR, intraoperative succinyl gelatin infusion and major hepatectomy. A three-factor prediction model was successfully established for predicting the PAC after hepatectomy.

The safety and efficacy of Sotn ureteroscopy for renal and upper ureteral calculi: a prospective multicenter randomized controlled trial.

BACKGROUND: Sotn ureteroscopy is a new lithotripsy procedure developed on the basis of ureteroscopy and includes a rigid ureteral access sheath, standard mirror, lithotripsy mirror, and Sotn perfusion aspirator. Thus, we performed a prospective multicenter randomized controlled trial comparing the safety and efficacy of Sotn ureteroscopy in the treatment of renal and upper ureteral calculi. METHODS: In this study, 224 patients with renal and upper ureteral calculi were randomly divided equally into study and control groups from March 2018 to March 2022. All the patients were approved by the hospital ethics committee (proof number: ZF-2018-164-01 and ZF-2018-165-01) of the Second Affiliate Hospital of Guangzhou University of Chinese Medicine in China. The primary outcome was stone-free rate (SFR) assessed by computed tomography on the 1st day and month after treatment and operation duration. The secondary outcome was postoperative complication rate. RESULTS: In total, for upper ureteral calculi, the SFR of 1 day after operation of the Sotn ureteroscopy group was significantly higher than the rigid ureteroscopy group (83.6% vs. 60%, P=0.006). Moreover, operative time (33.7±1.80 vs. 52.9±2.73 min, P<0.005) of the Sotn ureteroscopy group was significantly lower than the rigid ureteroscopy group. Additionally, the SFR of 1 day after operation and operative time for the study group (Sotn ureteroscopy combined with flexible ureteroscopy) and the control group (flexible ureteroscopy alone) were 63.2% and 36.8% (P=0.005), 65.6±4.06 and 80.3±4.91 (P=0.023), respectively. However, there were no significant differences in the SFR of 1 month after operation, success rate of ureteral access sheath placement, and postoperative complications between the two groups (P>0.05). In subgroups with stone diameters ≥1.5 cm and stone CT values ≥1000 Hounsfield units, Sotn ureteroscopy showed more advantages in terms of the SFR of 1 day after operation. Importantly, complications such as ureteral injury, sepsis, fever, and severe hematuria were not statistically different between the two groups (P>0.05). CONCLUSIONS: For renal and upper ureteral calculi, Sotn ureteroscopy has the advantage of a higher SFR of 1 day after the operation and a shorter operative time, suggesting that the Sotn ureteroscopy may have further potential applications in clinics.

Two-dimensional Janus Polarization Functioned by Mechanical Force.

Two-dimensional (2D) polarization materials have emerged as promising candidates for meeting the demands of device miniaturization, attributed to their unique electronic configurations and transport characteristics. Although the existing inherent and sliding mechanisms have been increasingly investigated in recent years, strategies for inducing 2D polarization with innovative mechanisms remain rare. In this study, we introduce a novel 2D Janus state by modulating the puckered structure. Combining scanning probe microscopy, transmission electron microscopy, and density functional theory calculations, we realized force-triggered out-of-plane and in-plane dipoles with distorted smaller warping in GeSe. The Janus state is preserved after removing the external mechanical perturbation, which could be switched by modulating the sliding direction. Our work offers a versatile method to break the space inversion symmetry in a 2D system to trigger polarization in the atomic scale, which may open an innovative insight into configuring novel 2D polarization materials. This article is protected by copyright. All rights reserved.

Assessing agricultural greenhouse gas emission mitigation by scaling up farm size: An empirical analysis based on rural household survey data.

Agriculture is a major contributor to greenhouse gas (GHG) emissions. Farm size affects agricultural production inputs and thus has impacts on agricultural GHG emissions. However, the effects and mechanisms behind this are still unclear. In this paper, we identified the effects and mechanisms of farm size on agricultural GHG emissions, based on survey data about over 20,000 rural households in China from 2009 to 2016. Firstly, we calculated the agricultural CO2, CH4, and N2O emissions using the life-cycle analysis (LCA). Secondly, the impacts of farm size on GHG emissions intensity were explored with a fixed effect model, based on the long-term rural household survey data. Finally, the mechanisms were tested by the mediation effect model. The results showed that a 1 % increase in farm size, on average, could reduce the GHG emissions intensity of rural households by 0.245 % from 2009 to 2016. The mechanism analysis showed that the larger farm size reduced GHG emissions intensity mainly by reducing the non-fixed input intensity and raising fixed input investment. By identifying the impacts and mechanisms of farm size on agricultural GHG emissions, this paper aims to provide insights for policymakers to achieve China's goal of reaching carbon neutrality by 2060.

Oral vitamin A supplements to prevent acute upper respiratory tract infections in children up to seven years of age.

BACKGROUND: According to global prevalence analysis studies, acute upper respiratory tract infections (URTIs) are the most common acute infectious disease in children, especially in preschool children. Acute URTIs lead to an economic burden on families and society. Vitamin A refers to the fat-soluble compound all-trans-retinol and also represents retinol and its active metabolites. Vitamin A interacts with both the innate immune system and the adaptive immune system and improves the host's defences against infections. Correlation studies show that serum retinol deficiency was associated with a higher risk of respiratory tract infections. Therefore, vitamin A supplementation may be important in preventing acute URTIs. OBJECTIVES: To assess the effectiveness and safety of vitamin A supplements for preventing acute upper respiratory tract infections in children up to seven years of age. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the Chinese Biomedical Literature Database, and two trial registration platforms to 8 June 2023. We also checked the reference lists of all primary studies and reviewed relevant systematic reviews and trials for additional references. We imposed no language or publication restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs), which evaluated the role of vitamin A supplementation in the prevention of acute URTIs in children up to seven years of age. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included six studies (27,351 participants). Four studies were RCTs and two were cluster-RCTs. The included studies were all conducted in lower-middle-income countries (two in India, two in South Africa, one in Ecuador, and one in Haiti). Three studies included healthy children who had no vitamin A deficiency, one study included children born to HIV-infected women, one study included low-birthweight neonates, and one study included children in areas with a high local prevalence of malnutrition and xerophthalmia. In two studies, vitamin E was a co-treatment administered in addition to vitamin A. We judged the included studies to be at either a high or unclear risk of bias for random sequence generation, incomplete outcome data, and blinding. Primary outcomes Six studies reported the incidence of acute URTIs during the study period. Five studies reported the number of acute URTIs over a period of time, but there was population heterogeneity and the results were presented in different forms, therefore only three studies were meta-analysed. We are uncertain of the effect of vitamin A supplementation on the number of acute URTIs over two weeks (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.92 to 1.09; I2 = 44%; 3 studies, 22,668 participants; low-certainty evidence). Two studies reported the proportion of participants with an acute URTI. We are uncertain of the effect of vitamin A supplementation on the proportion of participants with an acute URTI (2 studies, 15,535 participants; low-certainty evidence). Only one study (116 participants) reported adverse events. No infant in either the placebo or vitamin A group was found to have feeding difficulties (failure to feed or vomiting), a bulging fontanelle, or neurological signs before or after vitamin A administration (very low-certainty evidence). Secondary outcomes Two studies (296 participants) reported the severity of subjective symptoms, presented by the mean duration of acute URTI. Vitamin A may have little to no effect on the mean duration of acute URTI (very low-certainty evidence). AUTHORS' CONCLUSIONS: The evidence for the use of vitamin A supplementation to prevent acute URTI is uncertain, because population, dose and duration of interventions, and outcomes vary between studies. From generally very low- to low-certainty evidence, we found that there may be no benefit in the use of vitamin A supplementation to prevent acute URTI in children up to seven years of age. More RCTs are needed to strengthen the current evidence. Future research should report over longer time frames using validated tools and consistent reporting, and ensure adequate power calculations, to allow for easier synthesis of data. Finally, it is important to assess vitamin A supplementation for preschool children with vitamin A deficiency.

A Scoping Review of the Epidemiology, Management, and Outcomes of Golf-Related Fractures.

ABSTRACT: Golf is a popular sport; however, there is a paucity of data in relation to golf-associated fractures, and the rate and timing of returning to golf. The aim of this review is to describe golf-associated fractures, including epidemiology, management, and timing of returning to golf following treatment. A literature search was performed using MEDLINE/PubMed, Embase, and Web of Science. Data were extracted and summarized in a narrative synthesis. A total of 436 articles were identified with an initial search of which 58 met the inclusion criteria. Twelve anatomical sites of golf swing-related fractures were identified, of which 10 sites were specific for stress fractures. The most common sites of golf swing-related stress fractures were the ribs followed by the hook of hamate. There was a common theme of delay to diagnosis, being initially assigned to a soft tissue injury. Most golfers with swing-related stress fractures were able to return to golf with the exception of osteoporotic associated vertebral stress fractures. Timing of returning to golf was between 4 and 12 months for most of the golfers with stress fractures following conservative management. Operative intervention was an option of hook of hamate nonunion, following a stress fracture, and tibial shaft stress fractures. Golf equipment-related fractures were not rare and were associated with major trauma and in some cases associated with significant persistent morbidity. Golf-related stress fractures commonly involve the ribs and hook of hamate; knowledge of this may aid in early diagnosis and appropriate treatment when symptomatic golfers are encountered. Although golf is a noncontact sport, fractures associated with golf equipment can be life changing, and safety training guidelines should be established.

Photocatalytic Generation of Carbocation from Thiols and Application to Cross-Nucleophile Coupling.

Represented herein is a simple thiol identified as an effective precursor to photochemically form a carbocation. Thanks to the thiyl radical rapid transformation to disulfide, which serves not only to stabilize the generated thiyl radical but also to allow the second electron transfer to form a carbocation. The resulting carbocations, including primary benzylic, secondary, and tertiary carbocations, can smoothly couple with nitrogen, oxygen, and carbon nucleophilic coupling partners as well as complex drug molecules, accompanied by elemental sulfur formation in air.

Modular Access to Chiral Amines via Imine Reductase-Based Photoenzymatic Catalysis.

The development of catalysts serves as the cornerstone of innovation in synthesis, as exemplified by the recent discovery of photoenzymes. However, the repertoire of naturally occurring enzymes repurposed by direct light excitation to catalyze new-to-nature photobiotransformations is currently limited to flavoproteins and keto-reductases. Herein, we shed light on imine reductases (IREDs) that catalyze the remote C(sp3)-C(sp3) bond formation, providing a previously elusive radical hydroalkylation of enamides for accessing chiral amines (45 examples with up to 99% enantiomeric excess). Beyond their natural function in catalyzing two-electron reductive amination reactions, upon direct visible-light excitation or in synergy with a synthetic photoredox catalyst, IREDs are repurposed to tune the non-natural photoinduced single-electron radical processes. By conducting wet mechanistic experiments and computational simulations, we unravel how engineered IREDs direct radical intermediates toward the productive and enantioselective pathway. This work represents a promising paradigm for harnessing nature's catalysts for new-to-nature asymmetric transformations that remain challenging through traditional chemocatalytic methods.

Pan-cancer analysis of prognostic and immunological role of IL4I1 in human tumors: a bulk omics research and single cell sequencing validation.

BACKGROUND: Interleukin-4 inducible gene 1 (IL4I1) regulates tumor progression in numerous tumor types. However, its correlation with immune infiltration and prognosis of patients in a pan-cancer setting remains unclear. METHODS: Data from the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), UALCAN, Clinical Proteomic Tumor Analysis Consortium (CPTAC), Gene Expression Omnibus (GEO), cBioPortal, Cancer Single-cell State Atlas (CancerSEA), and Tumor IMmune Estimation Resource(TIMER) databases were used to evaluate IL4I1 expression, clinical features and prognostic effects, gene set enrichment, and correlation with immune cell infiltration, as well as the relationship between IL4I1 methylation and expression and survival prognosis. Correlations with 192 anticancer drugs were also analyzed. RESULTS: IL4I1 was significantly overexpressed in the majority of tumors, and the imbalance of IL4I1 was significantly correlated with overall survival and pathological stage. Moreover, total IL4I1 protein was increased in cancer. Therefore, IL4I1 may be used as a prognostic biomarker or protective factor in numerous types of cancer. The methylation level of IL4I1 may also be used as a prognostic marker. The functional enrichment of IL4I1 was closely related to the immunomodulatory pathway. In addition, the level of tumor-associated macrophage infiltration was positively correlated with the expression of IL4I1 in pan-cancerous tissues. scRNA-seq analysis suggested that IL4I1 differ significantly among different cells in the tumor microenvironment and was most enriched in macrophages. Various immune checkpoint genes were positively correlated with IL4I1 expression in most tumors. In addition, patients with high IL4I1 expression may be resistant to BMS-754807 and docetaxel, but sensitive to temozolomide. CONCLUSION: IL4I1 may play a role as promoter of cancer and prognostic indicator in patients. High expression of IL4I1 is associated with the state of tumor immunosuppression and may contribute to tumor-associated macrophage invasion. Therefore, IL4I1 may be a new therapeutic target for the treatment and prognosis of patients with cancer.

Polarized M2 macrophages induced by glycosylated nano-hydroxyapatites activate bone regeneration in periodontitis therapy.

AIM: To investigate the association between periodontal macrophage polarization states and the alveolar bone levels, and to assess whether glycosylated nano-hydroxyapatites (GHANPs) could improve bone regeneration in periodontitis by inducing macrophage M2 polarization. MATERIALS AND METHODS: The change of macrophage polarization state in inflammatory periodontal tissues (with bone loss) was examined using clinical gingival samples. The relationship between macrophage phenotype and bone level in periodontal bone loss and repair was evaluated using a mouse periodontitis model. The effect of GHANPs on macrophage polarization was assessed by the in vitro model of lipopolysaccharide (LPS)-stimulated inflammation. The polarization-related markers were detected by immunofluorescence staining, real-time polymerase chain reaction and enzyme-linked immunosorbent assay analysis. The therapeutic effect of GHANPs on alveolar bone loss was explored in experimental periodontitis by histological staining and micro-CT analysis. RESULTS: A lower macrophage M2/M1 ratio was observed in periodontitis-affected human gingival tissues. The results of animal experiments demonstrated a positive correlation between a lower Arg-1/iNOS ratio and accelerated alveolar bone loss; also, the proportion of Arg-1-positive macrophages increased during bone repair and regeneration. The administration of GHANPs partially restored M2 macrophage polarization after LPS stimulation. GHANPs increased alveolar bone repair and regeneration in experimental periodontitis induced by ligation, potentially related to their macrophage M2 transition regulation. CONCLUSIONS: The findings of this study indicate that the induction of macrophage M2 polarization can be considered a viable approach for enhancing inflammatory bone repair. Additionally, GHANPs show potential in the clinical treatment of periodontitis.

Photodynamic therapy for the treatment of port-wine stains in phakomatosis pigmentovascularis.

BACKGROUND: Phakomatosis pigmentovascularis (PPV) is a rare congenital syndrome. Only a few studies have reported the treatment of PPV, including a case using photodynamic therapy (PDT) to treat PPV-associated port-wine stains (PWS). OBJECTIVE: To investigating the efficacy and adverse effects of hemoporfin-PDT in PPV-associated PWS. METHODS: The efficacy and adverse effects in patients with PPV who underwent two sessions of hemoporfin-PDT from January 2019 to December 2022 were retrospectively analyzed. RESULTS: Twenty patients were included (13 females, 7 males, age range: 2-31 years; mean: 8.20 ± 8.92 years). Two, nine, seven, and two patients had PPV types Ia, IIa, IIb, and IIIa, respectively. After two treatments, the visual evaluation indicated the color of the PWS in 4, 5, 6, and 5 patients showed poor, fair, good, and excellent improvements, respectively. The combined good and excellent improvement rates in patients with PWS and pigmentary nevus overlapping in the same treatment area and in patients with PWS in the treatment areas only were 33.3% versus 87.5%, respectively, and were significantly different (p = 0.02). Minor side effects, such as edema, scabbing, hyperpigmentation, and blistering, were observed in some patients after PDT. CONCLUSION: Hemoporfin-PDT is an effective treatment for PPV-associated PWS. Patients with PWS and pigmentary nevus overlapping in the same treatment area showed poorer efficacy than patients with PWS in the treatment areas only.

Identification of extracellular polymeric substances layer barrier in chloroquine phosphate-disturbed anammox consortia and mechanism dissection on cytotoxic behavior by computational chemistry.

The over-dosing use of chloroquine phosphate (CQ) poses severe threats to human beings and ecosystem due to the high persistence and biotoxicity. The discharge of CQ into wastewater would affect the biomass activity and process stability during the biological processes, e.g., anammox. However, the response mechanism of anammox consortia to CQ remain unknown. In this study, the accurate role of extracellular polymeric substances barrier in attenuating the negative effects of CQ, and the mechanism on cytotoxic behavior were dissected by molecular spectroscopy and computational chemistry. Low concentrations (≤6.0 mg/L) of CQ hardly affected the nitrogen removal performance due to the adaptive evolution of EPS barrier and anammox bacteria. Compact protein of EPS barrier can bind more CQ (0.24 mg) by hydrogen bond and van der Waals force, among which O-H and amide II region respond CQ binding preferentially. Importantly, EPS contributes to the microbiota reshape with selectively enriching Candidatus_Kuenenia for self-protection. Furthermore, the macroscopical cytotoxic behavior was dissected at a molecular level by CQ fate/distribution and computational chemistry, suggesting that the toxicity was ascribed to attack of CQ on functional proteins of anammox bacteria with atom N17 (f-=0.1209) and C2 (f+=0.1034) as the most active electrophilic and nucleophilic sites. This work would shed the light on the fate and risk of non-antibiotics in anammox process.

Hsa_circ_0101050 accelerates the progression of Colon cancer by targeting the miR-140-3 p/MELK axis.

BACKGROUND: Circular RNAs (circRNAs) are involved in the progression of colon cancer (CC). This study aimed to examine the role of a new circRNA circ_0101050 in CC. METHODS: Dual-luciferase reporter and RNA immunoprecipitation analyses were performed to validate the target relationships among maternal embryonic leucine zipper kinase (MELK), microRNA (miR)-140-3 p, and circ_0101050. Expression levels were calculated using western blotting and/or quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blotting was performed to evaluate the relative expression of Bcl-2 and Bax proteins to determine cell death. Cell Counting Kit-8 (CCK-8) and colony formation assays were performed to determine the proliferative potential of CC cells. The migration rate of CC cells was evaluated using wound healing assays. Tumor formation tests were performed to determine the effect of circ_0101050 on tumor development in vivo. RESULTS: Elevated levels of circ_0101050 and MELK were observed in CC. By inhibiting circ 0,101,050 or MELK, CC cell proliferation and migration were inhibited, but CC cell apoptosis was promoted. Silencing circ_0101050 also inhibited CC growth in vivo. We also found that miR-140-3 p was downregulated, which alleviated the repressive effects of circ_0101050 knockdown on proliferating and migrating CC cells, as well as the stimulating effect on apoptosis. In addition, the absence of MELK alleviated the effects of miR-140-3 p downregulation, which enhanced CC cell malignancy. CONCLUSIONS: Circ_0101050 exacerbates malignant phenotypes in CC by targeting the miR-140-3 p/MELK axis. These findings suggested that the circ_0101050/miR-140-3 p/MELK network may be a prospective target for CC treatment.

Boosting the Carrier Lifetime and Optical Activity of CsPbX3 Nanocrystals through Aromatic Ligand Passivation.

Ligand engineering is crucial for tuning the structural and optoelectronic properties of perovskite nanocrystals (NCs), which also improves their stability. In contrast to the typically used long-chain alkylamine ligands, we successfully introduced an aromatic 1-(p-tolyl)ethylamine (PTEA) ligand to synthesize the CsPbX3 (X = Br or I) NCs. The CsPbI3 and CsPbBr3 NCs demonstrated long carrier lifetimes of ∼877 and 49 ns, respectively, as well as high photoluminescence quantum yields (PLQYs) of ∼99% and 95%, respectively. Furthermore, such NCs realized excellent long-term stability in an ambient atmosphere without obvious degradation over one month. All of these properties were better than the properties of NCs coated with the conventional alkylamine ligands. The high performance of these NCs was discussed with the effective surface passivation by PTEA. Our finding suggests a facile and effective ligand (PTEA) for modulating perovskites, achieving enhancement of both the carrier lifetime and the PLQY.

Effectiveness of Blended Versus Traditional Refresher Training for Cardiopulmonary Resuscitation: Prospective Observational Study.

BACKGROUND: Generally, cardiopulmonary resuscitation (CPR) skills decline substantially over time. By combining web-based self-regulated learning with hands-on practice, blended training can be a time- and resource-efficient approach enabling individuals to acquire or refresh CPR skills at their convenience. However, few studies have evaluated the effectiveness of blended CPR refresher training compared with that of the traditional method. OBJECTIVE: This study investigated and compared the effectiveness of traditional and blended CPR training through 6-month and 12-month refresher sessions with CPR ability indicators. METHODS: This study recruited participants aged ≥18 years from the Automated External Defibrillator Donation Project. The participants were divided into 4 groups based on the format of the CPR training and refresher training received: (1) initial traditional training (a 30-minute instructor-led, hands-on session) and 6-month traditional refresher training (Traditional6 group), (2) initial traditional training and 6-month blended refresher training (an 18-minute e-learning module; Mixed6 group), (3) initial traditional training and 12-month blended refresher training (Mixed12 group), and (4) initial blended training and 6-month blended refresher training (Blended6 group). CPR knowledge and performance were evaluated immediately after initial training. For each group, following initial training but before refresher training, a learning effectiveness assessment was conducted at 12 and 24 months. CPR knowledge was assessed using a written test with 15 multiple-choice questions, and CPR performance was assessed through an examiner-rated skill test and objectively through manikin feedback. A generalized estimating equation model was used to analyze changes in CPR ability indicators. RESULTS: This study recruited 1163 participants (mean age 41.82, SD 11.6 years; n=725, 62.3% female), with 332 (28.5%), 270 (23.2%), 258 (22.2%), and 303 (26.1%) participants in the Mixed6, Traditional6, Mixed12, and Blended6 groups, respectively. No significant between-group difference was observed in knowledge acquisition after initial training (P=.23). All groups met the criteria for high-quality CPR skills (ie, average compression depth: 5-6 cm; average compression rate: 100-120 beats/min; chest recoil rate: >80%); however, a higher proportion (98/303, 32.3%) of participants receiving blended training initially demonstrated high-quality CPR skills. At 12 and 24 months, CPR skills had declined in all the groups, but the decline was significantly higher in the Mixed12 group, whereas the differences were not significant between the other groups. This finding indicates that frequent retraining can maintain high-quality CPR skills and that blended refresher training is as effective as traditional refresher training. CONCLUSIONS: Our findings indicate that 6-month refresher training sessions for CPR are more effective for maintaining high-quality CPR skills, and that as refreshers, self-learning e-modules are as effective as instructor-led sessions. Although the blended learning approach is cost and resource effective, factors such as participant demographics, training environment, and level of engagement must be considered to maximize the potential of this approach. TRIAL REGISTRATION: IGOGO NCT05659108; https://www.cgmh-igogo.tw.

Deepening genomic sequences of 1081 Gossypium hirsutum accessions reveals novel SNPs and haplotypes relevant for practical breeding utility.

Fiber quality is a major breeding goal in cotton, but phenotypically direct selection is often hindered. In this study, we identified fiber quality and yield related loci using GWAS based on 2.97 million SNPs obtained from 10.65× resequencing data of 1081 accessions. The results showed that 585 novel fiber loci, including two novel stable SNP peaks associated with fiber length on chromosomes At12 and Dt05 and one novel genome regions linked with fiber strength on chromosome Dt12 were identified. Furthermore, by means of gene expression analysis, GhM_A12G0090, GhM_D05G1692, GhM_D12G3135 were identified and GhM_D11G2208 function was identified in Arabidopsis. Additionally, 14 consistent and stable superior haplotypes were identified, and 25 accessions were detected as possessing these 14 superior haplotype in breeding. This study provides fundamental insight relevant to identification of genes associated with fiber quality and yield will enhance future efforts toward improvement of upland cotton.