Development of an instrument to measure the competencies of health professionals in the process of evidence-based healthcare: A Delphi study.

AIMS: To identify and reach consensus on dimensions and criteria of a competence assessment instrument for health professionals in relation to the process of evidence-based healthcare. DESIGN: A two-round Delphi survey was carried out from April to June 2023. METHODS: Consensus was sought from an expert panel on the instrument preliminarily established based on the JBI Model of Evidence-Based Healthcare and a rapid review of systematic reviews of relevant literature. The level of consensus was reflected by the concentration and coordination of experts' opinions and percentage of agreement. The instrument was revised significantly based on the combination of data analysis, the experts' comments and research group discussions. RESULTS: Sixteen national and three international experts were involved in the first-round Delphi survey and 17 experts participated in the second-round survey. In both rounds, full consensus was reached on the four dimensions of the instrument, namely evidence-generation, evidence-synthesis, evidence-transfer and evidence-implementation. In round-one, the instrument was revised from 77 to 61 items. In round-two, the instrument was further revised to have 57 items under the four dimensions in the final version. CONCLUSION: The Delphi survey achieved consensus on the instrument. The validity and reliability of the instrument needs to be tested in future research internationally. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Systematic assessment of nurses and other health professionals' competencies in different phases of evidence-based healthcare process based on this instrument provides implications for their professional development and multidisciplinary team collaboration in evidence-based practice and better care process and outcomes. IMPACT: This study addresses a research gap of lacking an instrument to systematically assess interprofessional competencies in relation to the process of EBHC. The instrument covers the four phases of EBHC process with minimal criteria, highlighting essential aspects of ability to be developed. Identification of health professionals' level of competence in these aspects helps strengthen their capacity accordingly so as to promote virtuous EBHC ecosystem for the ending purpose of improving global healthcare outcomes. REPORTING METHOD: This study was reported in line with the Conducting and REporting of DElphi studies (CREDES) guidance on Delphi studies. PATIENT AND PUBLIC CONTRIBUTION: No patient or public contribution.

The E2F family: a ray of dawn in cardiomyopathy.

Cardiomyopathies are a group of heterogeneous diseases, characterized by abnormal structure and function of the myocardium. For many years, it has been a hot topic because of its high morbidity and mortality as well as its complicated pathogenesis. The E2Fs, a group of transcription factors found extensively in eukaryotes, play a crucial role in governing cell proliferation, differentiation, and apoptosis, meanwhile their deregulated activity can also cause a variety of diseases. Based on accumulating evidence, E2Fs play important roles in cardiomyopathies. In this review, we describe the structural and functional characteristics of the E2F family and its role in cardiomyocyte processes, with a focus on how E2Fs are associated with the onset and development of cardiomyopathies. Moreover, we discuss the great potential of E2Fs as biomarkers and therapeutic targets, aiming to provide a reference for future research.

Ji-Ni-De-Xie ameliorates type 2 diabetes mellitus by modulating the bile acids metabolism and FXR/FGF15 signaling pathway.

Introduction: Ji-Ni-De-Xie (JNDX) is a traditional herbal preparation in China. It is widely used to treat type 2 diabetes mellitus (T2DM) in traditional Tibetan medicine system. However, its antidiabetic mechanisms have not been elucidated. The aim of this study is to elucidate the underlying mechanism of JNDX on bile acids (BAs) metabolism and FXR/FGF15 signaling pathway in T2DM rats. Methods: High-performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-QQQ-MS) and UPLC-Q-Exactive Orbitrap MS technology were used to identify the constituents in JNDX. High-fat diet (HFD) combined with streptozotocin (45 mg∙kg-1) (STZ) was used to establish a T2DM rat model, and the levels of fasting blood-glucose (FBG), glycosylated serum protein (GSP), homeostasis model assessment of insulin resistance (HOMA-IR), LPS, TNF-α, IL-1ß, IL-6, TG, TC, LDL-C, HDL-C, and insulin sensitivity index (ISI) were measured to evaluate the anti-diabetic activity of JNDX. In addition, metagenomic analysis was performed to detect changes in gut microbiota. The metabolic profile of BAs was analyzed by HPLC-QQQ-MS. Moreover, the protein and mRNA expressions of FXR and FGF15 in the colon and the protein expressions of FGF15 and CYP7A1 in the liver of T2DM rats were measured by western blot and RT-qPCR. Results: A total of 12 constituents were identified by HPLC-QQQ-MS in JNDX. Furthermore, 45 chemical components in serum were identified from JNDX via UPLC-Q-Exactive Orbitrap MS technology, including 22 prototype components and 23 metabolites. Using a T2DM rat model, we found that JNDX (0.083, 0.165 and 0.33 g/kg) reduced the levels of FBG, GSP, HOMA-IR, LPS, TNF-α, IL-1ß, IL-6, TG, TC, and LDL-C, and increased ISI and HDL-C levels in T2DM rats. Metagenomic results demonstrated that JNDX treatment effectively improved gut microbiota dysbiosis, including altering some bacteria (e.g., Streptococcus and Bacteroides) associated with BAs metabolism. Additionally, JNDX improved BAs disorder in T2DM rats, especially significantly increasing cholic acid (CA) levels and decreasing ursodeoxycholic acid (UDCA) levels. Moreover, the protein and mRNA expressions of FXR and FGF15 of T2DM rats were significantly increased, while the expression of CYP7A1 protein in the liver was markedly inhibited by JNDX. Discussion: JNDX can effectively improve insulin resistance, hyperglycemia, hyperlipidemia, and inflammation in T2DM rats. The mechanism is related to its regulation of BAs metabolism and activation of FXR/FGF15 signaling pathway.

High-Resolution Spatiotemporal Modeling for PM2.5 Major Components in the Pearl River Delta and Its Implications for Epidemiological Studies.

Distinguishing the effects of different fine particulate matter components (PMCs) is crucial for mitigating their effects on human health. However, the sparse distribution of locations where PM is collected for component analysis makes it challenging to investigate the relevant health effects. This study aimed to investigate the agreement between data-fusion-enhanced exposure assessment and site monitoring data in estimating the effects of PMCs on gestational diabetes mellitus (GDM). We first improved the spatial resolution and accuracy of exposure assessment for five major PMCs (EC, OM, NO3-, NH4+, and SO42-) in the Pearl River Delta region by a data fusion model that combined inputs from multiple sources using a random forest model (10-fold cross-validation R2: 0.52 to 0.61; root mean square error: 0.55 to 2.26 µg/m3). Next, we compared the associations between exposures to PMCs during pregnancy and GDM in a hospital-based cohort of 1148 pregnant women in Heshan, China, using both site monitoring data and data-fusion model estimates. The comparative analysis showed that the data-fusion-based exposure generated stronger estimates of identifying statistical disparities. This study suggests that data-fusion-enhanced estimates can improve exposure assessment and potentially mitigate the misclassification of population exposure arising from the utilization of site monitoring data.

Therapeutic efficacy of recombinant human growth hormone in children with different etiologies of dwarfism from a pharmacoeconomic point of view.

Treatment outcomes for different causes of childhood dwarfism vary widely, and there are no studies on the economic burden of treatment in relation to outcomes. This paper compared the efficacy and healthcare costs per unit height of recombinant human growth hormone (rhGH) for the treatment of growth hormone deficiency (GHD) and idiopathic short stature (ISS) with a view to providing a more cost-effective treatment option for children. We retrospectively analyzed 117 cases (66 cases of GHD and 51 cases of ISS) of short-stature children who first visited Weifang People's Hospital between 2019.1 and 2022.1 and were treated with rhGH for 1 to 3 years to track the treatment effect and statistically analyzed by using paired t tests, non-parametric tests, and chi-square tests, to evaluate the efficacy of rhGH treatment for GHD and ISS children and the medicinal cost. The annual growth velocity (GV) of children with GHD and ISS increased the fastest during 3 to 6 months after treatment and then gradually slowed down. The GV of the GHD group was higher than that of the ISS group from 0 to 36 months after treatment (P < .05 at 3, 6, 9, and 12 months); the height standard deviation scores (HtSDS) of the children in the GHD and ISS groups increased gradually with the increase of the treatment time, and the changes in the height standard deviation scores (ΔHtSDS) of the GHD group were more significant than those of the ISS group (P < .05 at 3, 6, 9, and 12 months). (2) The medical costs in the pubertal group for a 1-cm increase in height were higher than those of children in the pre-pubertal group at the same stage (3 to 24 months P < .05). The longer the treatment time within the same group, the higher the medical cost of increasing 1cm height. RhGH is effective in treating children with dwarfism to promote height growth, and the effect on children with GHD is better than that of children with ISS; the earlier the treatment time, the lower the medical cost and the higher the comprehensive benefit.

Band Gap Renormalization at Different Symmetry Points in Perovskites.

Using ultrafast broad-band transient absorption (TA) spectroscopy of photoexcited MAPbBr3 thin films with probe continua in the visible and the mid- to deep-ultraviolet (UV) ranges, we capture the ultrafast renormalization at the fundamental gap at the R symmetry point of the Brillouin zone (BZ) and a higher energy gap at the M symmetry point. Advanced global lifetime analysis and lifetime density distribution analysis are applied to extract quantitative information. Our work confirms the similarity of the response at both high-symmetry points, which indicates a band edge renormalization that rises within the instrument response function (IRF, ∼250 fs) and decays in ca. 400-600 fs, undergoing an energy red shift of 90-150 meV. The reported time scale corresponds to the decay of free carriers into neutral excitons. The ability to monitor different high-symmetry points in photoexcited perovskites opens exciting prospects for the characterization of a large class of materials and for photonic applications.

When can we start early enteral nutrition safely in patients with shock on vasopressors?

Shock is a common critical illness characterized by microcirculatory disorders and insufficient tissue perfusion. Patients with shock and hemodynamic instability generally require vasopressors to maintain the target mean arterial pressure. Enteral nutrition (EN) is an important therapeutic intervention in critically ill patients and has unique benefits for intestinal recovery. However, the initiation of early EN in patients with shock receiving vasopressors remains controversial. Current guidelines make conservative and vague recommendations regarding early EN support in patients with shock. Increasing studies demonstrates that early EN delivery is safe and feasible in patients with shock receiving vasopressors; however, this evidence is based on observational studies. Changes in gastrointestinal blood flow vary by vasopressor and inotrope and are complex. The risk of gastrointestinal complications, especially the life-threatening complications of non-occlusive mesenteric ischemia and non-occlusive bowel necrosis, cannot be ignored in patients with shock during early EN support. It remains a therapeutic challenge in critical care nutrition therapy to determine the initiation time of EN in patients with shock receiving vasopressors and the safe threshold region for initiating EN with vasopressors. Therefore, the current review aimed to summarize the evidence on the optimal and safe timing of early EN initiation in patients with shock receiving vasopressors to improve clinical practice.

Dual cross-linked self-healing hydrogel enhanced by dopamine nanoparticles and raffinose for wound healing.

A series of intricate and dynamic physiological healing processes are involved in the healing of skin wounds. Herein, a multifunctional hydrogel is firstly designed and constructed by L-arginine-grafted O-carboxymethyl chitosan (CMCA), catechol-modified oxidized hyaluronic acid (DOHA), and dopamine nanoparticles (pDA-NPs). pDA-NPs were loaded in hydrogel for inherently powerful antimicrobial properties and could be as a cross-linking agent to construct hydrogels. Raffinose (Raf) was further incorporated to obtain CMCA-DOHA-pDA2@Raf hydrogel for its function of modulating epidermal differentiation. The hydrogel has good physicochemical properties and could promote cell proliferation and migration, which shows superior hemostatic capabilities in animal models of hemorrhage. The hydrogel significantly promoted wound healing on rat skin defect models by upregulating VEGF and CD31 and decreasing IL-6 and TNF-α, stimulating neovascularization and collagen deposition in epithelial structures. This multifunctional hydrogel implies the potential to be a dynamic wound dressing.

Comparative study the alleviated effects of various oligosaccharides on colitis in mice.

Oligosaccharides, namely, chitosan oligosaccharides (COS), fructooligosaccharides (FOS), and 2'-fucosyllactose (2-FL) were used to prevent the dextran sulfate sodium (DSS)-induced colitis in vivo based on antioxidant properties and anti-inflammatory activities, further comparing their alleviating effects to investigate the optimal anti-inflammatory agent. The results showed COS demonstrated the highest antioxidant properties, with a DPPH scavenging rate of 37.4% and an ABTS scavenging rate of 46.4% in these oligosaccharides. Consequently, COS exhibited the best anti-inflammatory activities on inflamed RAW 264.7 cells. Furthermore, the COS intervention demonstrated the best attenuated effects on decrease in the body weight and increase in DAI score, as well as on the overexpressed inflammatory factors and underexpressed short-chain fatty acids (SCFAs) compare to FOS and 2-FL. Therefore, these beneficial changes help prevent the damage to the inflammatory lesions in colonic histopathology. Additionally, COS significantly increased the diversity of gut microbiota and the ratio of Firmicutes/Bacteroidetes at phylum level. It also up-regulated the abundance of Lactobacillaceae and down-regulated Helicobacteraceae and Desulfovibrionaceae more effectively at family level to maintain oral tolerance against DSS. In short, COS intervention could be a promising nutritional strategy for alleviating colitis.

Engineering Spatially Adjacent Redox Sites with Synergistic Spin Polarization Effect to Boost Photocatalytic CO2 Methanation.

The integration of oxidation and reduction half-reactions to amplify their synergy presents a considerable challenge in CO2 photoconversion. Addressing this challenge requires the construction of spatially adjacent redox sites while suppressing charge recombination at these sites. This study introduces an innovative approach that utilizes spatial synergy to enable synergistic redox reactions within atomic proximity and employs spin polarization to inhibit charge recombination. We incorporate Mn into Co3O4 as a catalyst, in which Mn sites tend to enrich holes as water activation sites, while adjacent Co sites preferentially capture electrons to activate CO2, forming a spatial synergy. The direct H transfer from H2O at Mn sites facilitates the formation of *COOH on adjacent Co sites with remarkably favorable thermodynamic energy. Notably, the incorporation of Mn induces spin polarization in the system, significantly suppressing the recombination of photogenerated charges at redox sites. This effect is further enhanced by applying an external magnetic field. By synergizing spatial synergy and spin polarization, Mn/Co3O4 exhibits a CH4 production rate of 23.4 µmol g-1 h-1 from CO2 photoreduction, showcasing a 28.8 times enhancement over Co3O4. This study first introduces spin polarization to address charge recombination issues at spatially adjacent redox sites, offering novel insights for synergistic redox photocatalytic systems.

The association between O2-pulse slope ratio and functional severity of coronary stenosis: A combined cardiopulmonary exercise testing and quantitative flow ratio study.

Background: The role of cardiopulmonary exercise testing (CPET) parameters in evaluating the functional severity of coronary disease remains unclear. The aim of this study was to quantify the O2-pulse morphology and investigate its relevance in predicting the functional severity of coronary stenosis, using Murray law-based quantitative flow ratio (µQFR) as the reference. Methods: CPET and µQFR were analyzed in 138 patients with stable coronary artery disease (CAD). The O2-pulse morphology was quantified through calculating the O2-pulse slope ratio. The presence of O2-pulse plateau was defined according to the best cutoff value of O2-pulse slope ratio for predicting µQFR ≤ 0.8. Results: The optimal cutoff value of O2-pulse slope ratio for predicting µQFR ≤ 0.8 was 0.4, with area under the curve (AUC) of 0.632 (95 % CI: 0.505-0.759, p = 0.032). The total discordance rate between O2-pulse slope ratio and µQFR was 27.5 %, with 13 patients (9.4 %) being classified as mismatch (O2-pulse slope ratio > 0.4 and µQFR ≤ 0.8) and 25 patients being classified as reverse-mismatch (O2-pulse slope ratio ≤ 0.4 and µQFR > 0.8). Angiography-derived microvascular resistance was independently associated with mismatch (OR 0.07; 95 % CI: 0.01-0.38, p = 0.002) and reverse-mismatch (OR 9.76; 95 % CI: 1.47-64.82, p = 0.018). Conclusion: Our findings demonstrate the potential of the CPET-derived O2-pulse slope ratio for assessing myocardial ischemia in stable CAD patients.

Primary pancreatic peripheral T-cell lymphoma: A case report.

BACKGROUND: Primary pancreatic lymphoma (PPL) is an exceedingly rare tumor with limited mention in scientific literature. The clinical manifestations of PPL are often nonspecific, making it challenging to distinguish this disease from other pancreatic-related diseases. Chemotherapy remains the primary treatment for these individuals. CASE SUMMARY: In this case study, we present the clinical details of a 62-year-old woman who initially presented with vomiting, abdominal pain, and dorsal pain. On further evaluation through positron emission tomography-computed tomography, the patient was considered to have a pancreatic head mass. However, subsequent endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) revealed that the patient had pancreatic peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). There was a substantial decrease in the size of the pancreatic mass after the patient underwent a cycle of chemotherapy comprised of brentuximab vedotin, decitabine, and oxaliplatin (brentuximab vedotin and Gemox). The patient had significant improvement in radiological findings at the end of the first cycle. CONCLUSION: Primary pancreatic PTCL-NOS is a malignant and heterogeneous lymphoma, in which the clinical manifestations are often nonspecific. It is difficult to diagnose, and the prognosis is poor. Imaging can only be used for auxiliary diagnosis of other diseases. With the help of immunostaining, EUS-FNA could be used to aid in the diagnosis of PPL. After a clear diagnosis, chemotherapy is still the first-line treatment for such patients, and surgical resection is not recommended. A large number of recent studies have shown that the CD30 antibody drug has potential as a therapy for several types of lymphoma. However, identifying new CD30-targeted therapies for different types of lymphoma is urgently needed. In the future, further research on antitumor therapy should be carried out to improve the survival prognosis of such patients.

Successful ECMO treatment in patients with cerebral hemorrhage and PROC gene mutation associated with VTE: a case report.

In this report, we report a case of a middle-aged male, admitted to the ICU with cerebral hemorrhage resulting from a severe high-altitude fall. The patient encountered significant challenges in oxygenation index correction, attributed to extensive embolism in both the primary and branch pulmonary arteries. Consequently, the patient underwent an immediate initiation of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy, persisting for 20 days. During this treatment period, a mutation in the protein C (PROC) gene was identified. The medical team meticulously navigated the delicate balance between anticoagulation and bleeding risks. Eventually, the patient was successfully weaned off VA-ECMO and subsequently discharged. This report aims to delve into the etiology and therapeutic approaches of this uncommon case, with the intention of offering insightful reference for managing similar clinical scenarios in the future.

Efficient co-stabilization of arsenic and cadmium in farmland soil by schwertmannite under long-term flooding-drying condition.

Simultaneously stabilizing of arsenic (As) and cadmium (Cd) in co-contaminated soil presents substantial challenges due to their contrasting chemical properties. Schwertmannite (Sch) is recognized as a potent adsorbent for As pollution, with alkali modification showing promising results in the simultaneous immobilization of both As and Cd. This study systematically investigated the long-term stabilization efficacy of alkali-modified Sch in Cd-As co-contaminated farmland soil over a 200-day flooding-drying period. The results revealed that As showed significant mobility in flooded conditions, whereas Cd exhibited increased soil availability under drying phases. The addition of Sch did not affect the trends in soil pH and Eh fluctuations; nonetheless, it led to an augmentation in the levels of amorphous iron oxides and SO42- concentration in soil pore water. At a dosage of 0.5% Sch, there was a notable decrease in the mobility and soil availability of As and Cd under both flooding (34.5% and 53.6% at Day 50) and drying conditions (27.0% and 29.4% at Day 130), primarily promoting the transformation of labile metal(loid) fraction into amorphous iron oxide-bound forms. Throughout the flooding-drying treatment period, Sch maintained stable mineral morphology and mineralogical phase, highlighting its long-term stabilization effect. The findings of this study emphasize the promising application of Sch-based soil remediation agents in mitigating the challenges arising from As-Cd co-contamination. Further research is warranted to explore their application in real farmland settings and their impact on the uptake of toxic metal(loid)s by plants.

The association between PM2.5 components and blood pressure changes in late pregnancy: A combined analysis of traditional and machine learning models.

BACKGROUND: PM2.5 is a harmful mixture of various chemical components that pose a challenge in determining their individual and combined health effects due to multicollinearity issues with traditional linear regression models. This study aimed to develop an analytical methodology combining traditional and novel machine learning models to evaluate PM2.5's combined effects on blood pressure (BP) and identify the most toxic components. METHODS: We measured late-pregnancy BP of 1138 women from the Heshan cohort while simultaneously analyzing 31 PM2.5 components. We utilized multiple linear regression modeling to establish the relationship between PM2.5 components and late-pregnancy BP and applied Random Forest (RF) and generalized Weighted Quantile Sum (gWQS) regression to identify the most toxic components contributing to elevated BP and to quantitatively evaluate the cumulative effect of the PM2.5 component mixtures. RESULTS: The results revealed that 16 PM2.5 components, such as EC, OC, Ti, Fe, Mn, Cu, Cd, Mg, K, Pb, Se, Na+, K+, Cl-, NO3-, and F-, contributed to elevated systolic blood pressure (SBP), while 26 components, including two carbon components (EC, OC), fourteen metallics (Ti, Fe, Mn, Cr, Mo, Co, Cu, Zn, Cd, Na, Mg, Al, K, Pb), one metalloid (Se), and nine water-soluble ions (Na+, K+, Mg2+, Ca2+, NH4+, Cl-, NO3-, SO42-, F-), contributed to elevated diastolic blood pressure (DBP). Mn and Cr were the most toxic components for elevated SBP and DBP, respectively, as analyzed by RF and gWQS models and verified against each other. Exposure to PM2.5 component mixtures increased SBP by 1.04 mmHg (95% CI: 0.33-1.76) and DBP by 1.13 mmHg (95% CI: 0.47-1.78). CONCLUSIONS: Our study highlights the effectiveness of combining traditional and novel models as an analytical strategy to quantify the health effects of PM2.5 constituent mixtures.

Effects of short-term nitrogen and phosphorus addition on soil bacterial community of different halophytes.

Soil microbial community composition and diversity are often affected by nutrient enrichment, which may influence soil microbes to affect nutrient cycling and plant community structure. However, the response of soil bacteria to nitrogen (N) and phosphorus (P) addition and whether it is influenced by plants remains unclear. By 16S rRNA sequencing, we investigated the response of the rhizosphere and bulk soil bacterial communities of different halophytes (salt-rejecting, salt-absorbing, and salt-secreting plant) in the Yellow River Delta to short-term N and P addition. The response of rhizosphere bacterial diversity to N and P addition was opposite in Phragmites communis and Suaeda salsa. N addition increased the rhizosphere soil bacterial α-diversity of S. salsa and Aeluropus sinensis, while P addition decreased the rhizosphere bacterial α-diversity bacteria of S. salsa. The N and P addition had a weak effect on the rhizosphere bacterial community composition and a significant effect on the bulk soil bacterial community composition of halophytes. The S. salsa and P. communis bulk soil bacterial community were mainly influenced by P addition, while it was influenced by N addition in A. sinensis. N and P addition reduced the difference in bacterial community composition between the two types of soil. N and P addition increased the eutrophic taxa (Proteobacteria and Bacteroidetes) and decreased the oligotrophic taxa (Acidobacteria). Redundancy analysis showed that soil organic matter, salt, and total N content had significant effects on the bacterial community composition. The results clarify that the response of soil bacterial communities to N and P additions is inconsistent across the three halophyte soils, and the effect of plant species on the bacterial community was stronger than short-term N and P addition. IMPORTANCE: The bulk soil bacterial community was more affected by nutrient addition. Nitrogen (N) and phosphorus (P) have different effects on bacterial community. Soil organic matter is a key factor influencing the response of bacterial community to nutrient addition. N and P influence on bacterial community changes with plants.

A Novel Inhibitor of Poly(ADP-Ribose) Polymerase-1 Inhibits Proliferation of a BRCA-Deficient Breast Cancer Cell Line via the DNA Damage-Activated cGAS-STING Pathway.

Loss-of-function mutations in the Breast Cancer Susceptibility Gene (BRCA1 and BRCA2) are often detected in patients with breast cancer. Poly(ADP-ribose) polymerase-1 (PARP1) plays a key role in the repair of DNA strand breaks, and PARP inhibitors have been shown to induce highly selective killing of BRCA1/2-deficient tumor cells, a mechanism termed synthetic lethality. In our previous study, a novel PARP1 inhibitor─(E)-2-(2,3-dibromo-4,5-dimethoxybenzylidene)-N-(4-fluorophenyl) hydrazine-1-carbothioamide (4F-DDC)─was synthesized, which significantly inhibited PARP1 activity with an IC50 value of 82 ± 9 nM. The current study aimed to explore the mechanism(s) underlying the antitumor activity of 4F-DDC under in vivo and in vitro conditions. 4F-DDC was found to selectively inhibit the proliferation of BRCA mutant cells, with highly potent effects on HCC-1937 (BRCA1-/-) cells. Furthermore, 4F-DDC was found to induce apoptosis and G2/M cell cycle arrest in HCC-1937 cells. Interestingly, immunofluorescence and Western blot results showed that 4F-DDC induced DNA double strand breaks and further activated the cGAS-STING pathway in HCC-1937 cells. In vivo analysis results revealed that 4F-DDC inhibited the growth of HCC-1937-derived tumor xenografts, possibly via the induction of DNA damage and activation of the cGAS-STING pathway. In summary, the current study provides a new perspective on the antitumor mechanism of PARP inhibitors and showcases the therapeutic potential of 4F-DDC in the treatment of breast cancer.

The Response of Growth and Transcriptome Profiles of Tea Grey Blight Disease Pathogen Pestalotiopsis theae to the Variation of Exogenous L-Theanine.

Tea grey blight disease is one of the most destructive diseases that infects tea and is caused by the pathogen Pestalotiopsis theae (Sawada) Steyaert. L-theanine is a unique non-protein amino acid of the tea plant. Different concentrations of L-theanine exhibit significant inhibitory effects on the growth and sporulation ability of the pathogen causing tea grey blight disease. To understand the effect mechanism of L-theanine on P. theae, transcriptome profiling was performed on the pathogenic mycelium treated with three different concentrations of L-theanine: no L-theanine treatment (TH0), 20 mg/mL theanine treatment (TH2), and 40 mg/mL theanine treatment (TH4). The colony growths were significantly lower in the treatment with L-theanine than those without L-theanine. The strain cultured with a high concentration of L-theanine produced no spores or only a few spores. In total, 2344, 3263, and 1158 differentially expressed genes (DEGs) were detected by RNA-sequencing in the three comparisons, Th2 vs. Th0, Th4 vs. Th0, and Th4 vs. Th2, respectively. All DEGs were categorized into 24 distinct clusters. According to GO analysis, low concentrations of L-theanine primarily affected molecular functions, while high concentrations of L-theanine predominantly affected biological processes including external encapsulating structure organization, cell wall organization or biogenesis, and cellular amino acid metabolic process. Based on KEGG, the DEGs of Th2 vs. Th0 were primarily involved in pentose and glucuronate interconversions, histidine metabolism, and tryptophan metabolism. The DEGs of Th4 vs. Th0 were mainly involved in starch and sucrose metabolism, amino sugar, and nucleotide sugar metabolism. This study indicated that L-theanine has a significant impact on the growth and sporulation of the pathogen of tea grey blight disease and mainly affects amino acid metabolism, carbohydrate metabolism, and cellular structure-related biosynthesis processes of pathogenic fungi. This work provides insights into the direct control effect of L-theanine on pathogenic growth and also reveals the molecular mechanisms of inhibition of L-theanine to P. theae.

Disentangling Thermal from Electronic Contributions in the Spectral Response of Photoexcited Perovskite Materials.

Disentangling electronic and thermal effects in photoexcited perovskite materials is crucial for photovoltaic and optoelectronic applications but remains a challenge due to their intertwined nature in both the time and energy domains. In this study, we employed temperature-dependent variable-angle spectroscopic ellipsometry, density functional theory calculations, and broadband transient absorption spectroscopy spanning the visible to mid-to-deep-ultraviolet (UV) ranges on MAPbBr3 thin films. The use of deep-UV detection opens a new spectral window that enables the exploration of high-energy excitations at various symmetry points within the Brillouin zone, facilitating an understanding of the ultrafast responses of the UV bands and the underlying mechanisms governing them. Our investigation reveals that the photoinduced spectral features remarkably resemble those generated by pure lattice heating, and we disentangle the relative thermal and electronic contributions and their evolutions at different delay times using combinations of decay-associated spectra and temperature-induced differential absorption. The results demonstrate that the photoinduced transients possess a significant thermal origin and cannot be attributed solely to electronic effects. Following photoexcitation, as carriers (electrons and holes) transfer their energy to the lattice, the thermal contribution increases from ∼15% at 1 ps to ∼55% at 500 ps and subsequently decreases to ∼35-50% at 1 ns. These findings elucidate the intricate energy exchange between charge carriers and the lattice in photoexcited perovskite materials and provide insights into the limited utilization efficiency of photogenerated charge carriers.