Combination of radiotherapy and PD-L1 blockade induces abscopal responses in EGFR-mutated lung cancer through activating CD8+ T cells.

Patients with EGFR-mutated non-small cell lung cancer (NSCLC) respond poorly to immune checkpoint inhibitors (ICIs). It has been reported that the number of CD8+T cells is reduced in EGFR-mutated NSCLC. However, the extent of heterogeneity and effector function of distinct populations of CD8+T cells has not been investigated intensively. In addition, studies investigating whether a combination of radiotherapy and ICIs can improve the efficacy of ICIs in EGFR-mutated lung cancer are lacking. Single-cell RNA sequencing (scRNA-seq) was used to investigate the heterogeneity of CD8+T cell populations in EGFR-mutated NSCLC. The STING pathway was explored after hypofractionated radiation of EGFR-mutated and wild-type cells. Mice bearing LLC-19del and LLC-EGFR tumors were treated with radiotherapy plus anti-PD-L1. The scRNA-seq data showed the percentage of progenitor exhausted CD8+T cells was lower in EGFR-mutated NSCLC. In addition, CD8+T cells in EGFR-mutated NSCLC were enriched in oxidative phosphorylation. In EGFR-mutated and wild-type cells, 8 Gy × 3 increased the expression of chemokines that recruit T cells and activate the cGAS-STING pathway. In the LLC-19del and LLC-EGFR mouse model, the combination of radiation and anti-PD-L1 significantly inhibited the growth of abscopal tumors. The enhanced abscopal effect was associated with systemic CD8+T cell infiltration. This study provided an intensive understanding of the heterogeneity and effector functions of CD8+T cells in EGFR-mutated NSCLC. We showed that the combination of hypofractionated radiation and anti-PD-L1 significantly enhanced the abscopal responses in both EGFR-mutated and wild-type lung cancer by activating CD8+T cells in mice.

Accelerated Proton Transfer in Asymmetric Active Units for Sustainable Acidic Oxygen Evolution Reaction.

The poor durability of Ru-based catalysts limits the practical application in proton exchange membrane water electrolysis (PEMWE). Here, we report that the asymmetric active units in Ru1-xMxO2 (M = Sb, In, and Sn) binary solid solution oxides are constructed by introducing acid-resistant p-block metal sites, breaking the activity and stability limitations of RuO2 in acidic oxygen evolution reaction (OER). Constructing highly asymmetric Ru-O-Sb units with a strong electron delocalization effect significantly shortens the spatial distance between Ru and Sb sites, improving the bonding strength of the overall structure. The unique two-electron redox couples at Sb sites in asymmetric active units trigger additional chemical steps at different OER stages, facilitating continuous proton transfer. The optimized Ru0.8Sb0.2O2 solid solution requires a superlow overpotential of 160 mV at 10 mA cm-2 and a record-breaking stability of 1100 h in an acidic electrolyte. Notably, the scale-prepared Ru0.8Sb0.2O2 achieves efficient PEMWE performance under industrial conditions. General mechanism analysis shows that the enhanced proton transport in the asymmetric Ru-O-M unit provides a new working pathway for acidic OER, breaking the scaling relationship without sacrificing stability.

High-Performance Suspension Bead Sensor Based on Optical Tweezers and Immuno-Rolling Circle Amplification.

In recent years, optical tweezers have become an effective bioassay tool due to their unique advantages, especially in combination with suspension beads, which can be applied to develop a high-performance analysis platform capable of high-quality imaging and stable signal output. However, the optical tweezer-assisted bead analysis is still at the early stage, and further development of different favorable methods is in need. Herein, we have first developed the optical tweezer-assisted immuno-rolling circle amplification (immuno-RCA) on beads for protein detection. Prostate-specific antigen was selected as the model analyte, and the immunosandwich structure on beads was built by the high affinity of "antibody-antigen". The "protein-nucleic acid" signals were effectively converted through the covalent coupling procedure of antibodies and oligonucleotides, further initiating the RCA reaction to achieve signal amplification. The individual beads with the strong irregular Brownian motion in a fluid environment were eventually trapped by the optical tweezers to acquire the accurate and high-quality signal. Compared with the conventional immunoassay on beads, the sensitivity of the developed strategy was increased by 587 times with a limit of detection of 4.29 pg/mL (0.13 pM), as well as excellent specificity, stability, and reproducibility. This study developed the new optical tweezer-assisted beads imaging strategy for protein targets, which has great potential for being applied to clinical serology research and expands the application of optical tweezers in the bioassays.

Site-specific apparent optimum air temperature for vegetation photosynthesis across the globe.

The apparent optimum air temperature for vegetation photosynthesis (Topt) is a key temperature parameter in terrestrial ecosystem models estimating daily photosynthesis or gross primary production (GPP, g C/m2/day). To date, most models use biome-specific Topt (Topt-biome) parameter values. Given vegetation acclimation and adaptation to local climate, site-specific Topt (Topt-site) is needed to reduce uncertainties in estimating daily GPP across the scales from site to region and the globe. Previous studies have demonstrated using the Enhanced Vegetation Index (EVI) derived from Moderate Resolution Imaging Spectroradiometer (MODIS) images and daytime air temperature data to estimate the Topt-site at the eddy covariance tower sites. This study used MODIS-derived EVI and ERA5 climate data to estimate and generate global Topt-site data products from 2000 to 2019. The Topt-site of individual pixels within a biome has large variation, which clearly cannot be represented accurately by the widely used Topt-biome. Therefore, using this global dataset of Topt-site estimates might significantly affect GPP simulation in current ecosystem models.

Exploration of Berberine Against Ulcerative Colitis via TLR4/NF-κB/HIF-1α Pathway by Bioinformatics and Experimental Validation.

Purpose: This study aimed to delineate the molecular processes underlying the therapeutic effects of berberine on UC by employing network pharmacology tactics, molecular docking, and dynamic simulations supported by empirical validations both in vivo and in vitro. Patients and Methods: We systematically screened potential targets and relevant pathways affected by berberine for UC treatment from comprehensive databases, including GeneCards, DisGeNET, and GEO. Molecular docking and simulation protocols were used to assess the interaction stability between berberine and its principal targets. The predictions were validated using both a DSS-induced UC mouse model and a lipopolysaccharide (LPS)-stimulated NCM460 cellular inflammation model. Results: Network pharmacology analysis revealed the regulatory effect of the TLR4/NF-κB/HIF-1α pathway in the ameliorative action of berberine in UC. Docking and simulation studies predicted the high-affinity interactions of berberine with pivotal targets: TLR4, NF-κB, HIF-1α, and the HIF inhibitor KC7F2. Moreover, in vivo analyses demonstrated that berberine attenuates clinical severity, as reflected by decreased disease activity index (DAI) scores, reduced weight loss, and mitigated intestinal inflammation in DSS-challenged mice. These outcomes include suppression of the proinflammatory cytokines IL-6 and TNF-α and downregulation of TLR4/NF-κB/HIF-1α mRNA and protein levels. Correspondingly, in vitro findings indicate that berberine decreases cellular inflammatory injury and suppresses TLR4/NF-κB/HIF-1α signaling, with notable effectiveness similar to that of the HIF-1α inhibitor KC7F2. Conclusion: Through network pharmacology analysis and experimental substantiation, this study confirmed that berberine enhances UC treatment outcomes by inhibiting the TLR4/NF-κB/HIF-1α axis, thereby mitigating inflammatory reactions and improving colonic pathology.

Delivery of Lutein by Using Modified Burdock Polysaccharide Aggregates: Preparation, Characterization, and In Vitro Release Properties.

Novel self-assembled aggregates of stearic acid (SA)-modified burdock polysaccharide (BP) for loading lutein were constructed, and the release and absorption properties of lutein in the aggregates in simulated gastrointestinal fluid were investigated. Three different degrees of substitution (DS) of SA-BPs were used to embed lutein, resulting in the encapsulation efficiency exceeding 90%. The aggregates were uniformly spherical, with a particle size range of 227-341 nm. XRD analysis revealed that lutein was present in a non-crystalline state within the aggregates. FT-IR and FS analysis demonstrated that lutein was located in the hydrophobic domains of SA-BP. The highest bioavailability of lutein in these aggregates reached 4.36 times that in the unmodified samples. These aggregates were able to remain stable in gastric juice and enhance the release rate of lutein in intestinal fluid. The transport of lutein-loaded SA-BP aggregates in Caco-2 cells competed with P-glycoprotein inhibitors, mainly promoting the transmembrane absorption of lutein through caveolae (or lipid raft)-related and clathrin-dependent endocytosis pathways. The above results suggest that SA-BP aggregates have the potential to be promising carriers for the efficient delivery of hydrophobic lutein.

Characterizations of multi-kingdom gut microbiota in immune checkpoint inhibitor-treated hepatocellular carcinoma.

BACKGROUND: The association between gut bacteria and the response to immune checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC) has been studied; however, multi-kingdom gut microbiome alterations and interactions in ICI-treated HCC cohorts are not fully understood. METHODS: From November 2018 to April 2022, patients receiving ICI treatment for advanced HCC were prospectively enrolled. Herein, we investigated the multi-kingdom microbiota characterization of the gut microbiome, mycobiome, and metabolome using metagenomic, ITS2, and metabolomic data sets of 80 patients with ICI-treated HCC. RESULTS: Our findings demonstrated that bacteria and metabolites differed significantly between the durable clinical benefit (DCB) and non-durable clinical benefit (NDB) groups, whereas the differences were smaller for fungi. The overall diversity of bacteria and fungi before treatment was higher in the DCB group than in the NDB group, and the difference in diversity began to change with the use of immunotherapy after 6-8 weeks. We also explored the alterations of gut microbes in the DCB and NDB groups, established 18 bacterial species models as predictive biomarkers for predicting whether immunotherapy is of sustained benefit (area under the curve=75.63%), and screened two species of bacteria (Actinomyces_sp_ICM47, and Senegalimassilia_anaerobia) and one metabolite (galanthaminone) as prognostic biomarkers for predicting survival in patients with HCC treated with ICI. CONCLUSIONS: In this study, the status and characterization of the multi-kingdom microbiota, including gut bacteria, fungi, and their metabolites, were described by multiomics sequencing for the first time in patients with HCC treated with ICI. Our findings demonstrate the potential of bacterial taxa as predictive biomarkers of ICI clinical efficacy, and bacteria and their metabolites as prognostic biomarkers.

The impact of physical therapy on dysphagia in neurological diseases: a review.

A neurogenic dysphagia is dysphagia caused by problems with the central and peripheral nervous systems, is particularly prevalent in conditions such as Parkinson's disease and stroke. It significantly impacts the quality of life for affected individuals and causes additional burdens, such as malnutrition, aspiration pneumonia, asphyxia, or even death from choking due to improper eating. Physical therapy offers a non-invasive treatment with high efficacy and low cost. Evidence supporting the use of physical therapy in dysphagia treatment is increasing, including techniques such as neuromuscular electrical stimulation, sensory stimulation, transcranial direct current stimulation, and repetitive transcranial magnetic stimulation. While initial studies have shown promising results, the effectiveness of specific treatment regimens still requires further validation. At present, there is a lack of scientific evidence to guide patient selection, develop appropriate treatment regimens, and accurately evaluate treatment outcomes. Therefore, the primary objectives of this review are to review the results of existing research, summarize the application of physical therapy in dysphagia management, we also discussed the mechanisms and treatments of physical therapy for neurogenic dysphagia.

Gut microbiota and metabolites signatures of clinical response in anti-PD-1/PD-L1 based immunotherapy of biliary tract cancer.

BACKGROUND: Accumulating evidence suggests that the gut microbiota and metabolites can modulate tumor responses to immunotherapy; however, limited data has been reported on biliary tract cancer (BTC). This study used metagenomics and metabolomics to identify characteristics of the gut microbiome and metabolites in immunotherapy-treated BTC and their potential as prognostic and predictive biomarkers. METHODS: This prospective cohort study enrolled 88 patients with BTC who received PD-1/PD-L1 inhibitors from November 2018 to May 2022. The microbiota and metabolites significantly enriched in different immunotherapy response groups were identified through metagenomics and LC-MS/MS. Associations between microbiota and metabolites, microbiota and clinical factors, and metabolites and clinical factors were explored. RESULTS: Significantly different bacteria and their metabolites were both identified in the durable clinical benefit (DCB) and non-durable clinical benefit (NDB) groups. Of these, 20 bacteria and two metabolites were significantly associated with survival. Alistipes were positively correlated with survival, while Bacilli, Lactobacillales, and Pyrrolidine were negatively correlated with survival. Predictive models based on six bacteria, four metabolites, and the combination of three bacteria and two metabolites could all discriminated between patients in the DCB and NDB groups with high accuracy. Beta diversity between two groups was significantly different, and the composition varied with differences in the use of immunotherapy. CONCLUSIONS: Patients with BTC receiving immunotherapy have specific alterations in the interactions between microbiota and metabolites. These findings suggest that gut microbiota and metabolites are potential prognostic and predictive biomarkers for clinical outcomes of anti-PD-1/PD-L1-treated BTC.

Cold atmospheric plasma in combination with laser therapy provides a window for the treatment of hyperproliferative skin disease.

Modern medical understanding suggests that hyperproliferative skin diseases (HSDs) are complex syndromes characterized by localized hypertrophy or hyperplasia and infiltration of inflammatory cells. Various treatments, including systemic and topical pharmacotherapy, laser interventions, photodynamic therapy, and surgery, have been proposed for managing HSDs. However, challenges such as wound healing and recurrence after laser treatment have hindered the effectiveness of laser therapy. To overcome these challenges, we conducted a study combining laser therapy with cold atmospheric plasma (CAP) for the treatment of HSDs. Seven patients with different forms of HSDs, who had not responded well to conventional treatments, were enrolled in the study. These HSDs included cases of erythroplasia of Queyrat, pyoderma gangrenosum, keloids and hypertrophic scars, cellulitis, cutaneous lichen planus, and verruca vulgaris. Laser therapy was performed to remove the hyperplastic skin lesions, followed immediately by daily CAP treatment. The results were promising, with all patients successfully treated and no recurrence observed during the follow-up periods. The combined application of CAP and laser therapy proved to be an effective and complementary strategy for managing HSDs. This innovative approach provide evidence for addressing the limitation of laser therapy by utilizing CAP to promote wound healing and mitigate inflammatory responses. Chinese Clinical Trial Registry (ChiCTR2300069993).

A versatile dilution-treatment-detection microfluidic chip platform for rapid In vitro lung cancer drug combination sensitivity evaluation.

Combination drug therapy represents an effective strategy for treating certain drug-resistant and intractable cancer cases. However, determining the optimal combination of drugs and dosages is challenging due to clonal diversity in patients' tumors and the lack of rapid drug sensitivity evaluation methods. Microfluidic technology offers promising solutions to this issue. In this study, we propose a versatile microfluidic chip platform capable of integrating all processes, including dilution, treatment, and detection, for in vitro drug sensitivity assays. This platform innovatively incorporates several modules, including automated discrete drug logarithmic concentration generation, on-chip cell perfusion culture, and parallel drug treatments of cancer cell models. Moreover, it is compatible with microplate readers or high-content imaging systems for swift detection and automated monitoring, simplifying on-chip drug evaluation. Proof of concept is demonstrated by assessing the in vitro potency of two drugs, cisplatin, and etoposide, against the lung adenocarcinoma A549 cell line, under both single-drug and combination treatment conditions. The findings reveal that, compared to conventional microplate approaches with static cultivation, this on-chip automated perfusion bioassays yield comparable IC50 values with lower variation and a 50 % reduction in drug preparation time. This versatile dilution-treatment-detection microfluidic platform offers a promising tool for rapid and precise drug assessments, facilitating in vitro drug sensitivity evaluation in personalized cancer chemotherapy.

Assessment of drug-drug interaction of dapagliflozin with LCZ696 based on an LC-MS/MS method.

The co-administration of dapagliflozin (DPF) and sacubitril/valsartan (LCZ696) has emerged as a promising therapeutic approach for managing heart failure. Given that DPF and LCZ696 are substrates for P-glycoprotein, there is a plausible potential for drug-drug interactions when administered concomitantly. To investigate the pharmacokinetic changes when these drugs are co-administered, we have established and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method capable of simultaneously detecting DPF, LBQ657 (the active metabolite of sacubitril) and valsartan in rat plasma. This method has demonstrated selectivity, sensitivity, and accuracy. Drug-drug interactions were examined by the LC-MS/MS method. The mechanisms were investigated using everted intestinal sac models and Caco-2 cells. The results showed that DPF significantly increased the area under the curve (AUC(0-t)) (3,563.3 ± 651.7 vs. 7,146.5 ± 1,714.9 h µg/L) of LBQ657 (the active metabolite of sacubitril) and the AUC(0-t) (24,022.4 ± 6,774.3 vs. 55,728.3 ± 32,446.3 h µg/L) of valsartan after oral co-administration. Dapagliflozin significantly increased the amount of LBQ657 and valsartan in intestinal sacs by 1- and 1.25-fold at 2.25 h. Caco-2 cell uptake studies confirmed that P-glycoprotein is the transporter involved in this interaction. This finding enhances the understanding of drug-drug interactions in the treatment of heart failure and provides a guidence for clinical therapy.

The effect of mobile application-based technology on post-stroke aphasia: a systematic review.

Background: Enhancing speech-language therapy remains the most effective strategy for improving post-stroke aphasia, However, conventional face-to-face interventions often lack the necessary therapeutic intensity. In recent years, mobile application-based speech-language therapy has emerged progressively, offering new opportunities for independent rehabilitation among aphasic patients. This review aims to evaluate the impact of mobile application-based interventions on post-stroke aphasic. Methods: By conducting a systematic search across five databases (PubMed, Web of Science, EMBASE, CINAHL, and Scopus), we identified and included studies that investigated the utilization of mobile application-based technologies (such as computers, iPads, etc.) for treating post-stroke aphasia. Results: This study included 15 research investigations, including 10 randomized controlled trials (RCTs), four self-controlled studies and one cross-over experimental design study. Among these, eight studies demonstrated the efficacy of mobile application-based therapy in enhancing overall language functionality for post-stroke aphasia patients, three studies highlighted its potential for improving communication skills, three studies observed its positive impact on spontaneous speech expression. Moreover, four studies indicated its effectiveness in enhancing naming abilities, two studies underscored the positive influence of mobile application-based interventions on the quality of life for individuals with aphasia. Six studies noted that speech improvement effects were maintained during the follow-up period. Conclusion: The results of this review demonstrate the potential of mobile application-based interventions for improving speech-language function in individuals with aphasia. However, further high-quality research is needed to establish their effects across different domains and to delve into the comparative advantages of various treatment approaches. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=405248.

Transcatheter arterial perfusion chemotherapy combined with lipiodol chemoembolization for advanced colorectal cancer complicated by obstruction.

Background: Obstruction is a common complication of advanced colorectal cancer. This study was aimed at investigating the safety, efficacy, and feasibility of transcatheter arterial perfusion chemotherapy combined with lipiodol chemoembolization for treating advanced colorectal cancer complicated by obstruction. Patients and methods: This retrospective analysis was conducted using clinical data of patients with advanced colorectal cancer who received arterial infusion chemotherapy combined with lipiodol chemoembolization treatment at our center. Treatment efficacy was evaluated in terms of obstruction-free survival and overall survival, and treatment complications were monitored. Results: Fifty-four patients with colorectal cancer complicated by obstruction were included. All patients successfully underwent transcatheter arterial infusion combined with lipiodol chemoembolization treatment. The average lipiodol dose administered was 2.62 ± 1.45 ml (0.5-5.5 ml). No serious complications such as perforation or tumor dissemination occurred. The clinical success rate was 83.3% (45/54). One month after treatment, the objective response rate (ORR) and disease control rate (DCR) were 66.67% and 88.9%, respectively. The median obstruction-free survival was 5.0 months. No serious adverse events occurred. As of the last follow-up, 6 patients survived, 44 died, and 4 were lost to follow-up. Conclusion: Our findings revealed that transcatheter arterial infusion chemotherapy combined with lipiodol chemoembolization is safe and effective for treating advanced colorectal cancer complicated by obstruction. It may serve as a new treatment strategy for patients with advanced colorectal cancer complicated by obstruction.

High correlated color temperature artificial lighting impairs retinal pigment epithelium integrity and chloride ion transport: A potential mechanism for choroidal thinning.

Among the environmental factors contributing to myopia, the role of correlated color temperature (CCT) of ambient light emerges as a key element warranting in-depth investigation. The choroid, a highly vascularized and dynamic structure, often undergoes thinning during the progression of myopia, though the precise mechanism remains elusive. The retinal pigment epithelium (RPE), the outermost layer of the retina, plays a pivotal role in regulating the transport of ion and fluid between the subretinal space and the choroid. A hypothesis suggests that variations in choroidal thickness (ChT) may be modulated by transepithelial fluid movement across the RPE. Our experimental results demonstrate that high CCT illumination significantly compromised the integrity of tight junctions in the RPE and disrupted chloride ion transport. This functional impairment of the RPE may lead to a reduction in fluid transfer across the RPE, consequently resulting in choroidal thinning and potentially accelerating axial elongation. Our findings provide support for the crucial role of the RPE in regulating ChT. Furthermore, we emphasize the potential hazards posed by high CCT artificial illumination on the RPE, the choroid, and refractive development, underscoring the importance of developing eye-friendly artificial light sources to aid in the prevention and control of myopia.

Functional trait-based phytoplankton biomass and assemblage analyses in the pre-growing season for comprehensive algal bloom risk assessment.

Algal bloom (AB) risk assessment is critical for maintaining ecosystem health and human sustainability. Previous AB risk assessments have focused on the potential occurrence of ABs and related factors in the growing season, whereas their hazards, especially in the pre-growing season, have attracted less attention. Here, we performed a comprehensive AB risk assessment, including water trophic levels, phytoplankton biomass, functional trait-based assemblages, and related environmental factors, in the pre-growing season in Dongting Lake, China. Although mesotrophic water and low phytoplankton biomass suggested low AB potential, toxic taxa, which constituted 13.28% of the phytoplankton biomass, indicated non-negligible AB hazards. NH4+ and water temperature were key factors affecting phytoplankton motility and toxicity. Our study establishes a new paradigm for quantitative AB risk assessment, including both potential AB occurrence and hazards. We emphasize the importance of phytoplankton functional traits for early AB warning and NH4+ reduction for AB control in the pre-growing season.

Inhibiting Demetalation of Fe─N─C via Mn Sites for Efficient Oxygen Reduction Reaction in Zinc-Air Batteries.

Demetalation caused by the electrochemical dissolution of metallic Fe atoms is a major challenge for the practical application of Fe─N─C catalysts. Herein, an efficient single metallic Mn active site is constructed to improve the strength of the Fe─N bond, inhibiting the demetalation effect of Fe─N─C. Mn acts as an electron donor inducing more delocalized electrons to reduce the oxidation state of Fe by increasing the electron density, thereby enhancing the Fe─N bond and inhibiting the electrochemical dissolution of Fe. The oxygen reduction reaction pathway for the dissociation of Fe─Mn dual sites can overcome the high energy barriers to direct O─O bond dissociation and modulate the electronic states of Fe─N4 sites. The resulting FeMn─N─C exhibits excellent ORR activity with a high half-wave potential of 0.92 V in alkaline electrolytes. FeMn─N─C as a cathode catalyst for Zn-air batteries has a cycle stability of 700 h at 25 °C and a long cycle stability of more than 210 h under extremely cold conditions at -40 °C. These findings contribute to the development of efficient and stable metal-nitrogen-carbon catalysts for various energy devices.

Evaluation of the therapeutic efficacy of different doses of LT4 in pregnant women with high-normal TSH levels and TPOAb positivity in the first half of pregnancy.

BACKGROUND: The objective was to investigate the efficacy of different doses of levothyroxine therapy among pregnant women exhibiting high-normal thyroid stimulating hormone levels and positive thyroid peroxidase antibodies throughout the first half of pregnancy. METHODS: Pregnant women exhibiting high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positivity throughout the initial half of pregnancy were selected from January 2021 to September 2023. Based on the different doses of levothyroxine, the pregnant women were categorized into the nonintervention group (G0, 122 women), 25 µg levothyroxine intervention group (G25, 69 women), and 50 µg levothyroxine intervention group (G50, 58 women). Serum parameters, gastrointestinal symptoms, small intestinal bacterial overgrowth (SIBO), maternal and neonatal outcomes were compared after the intervention among the three groups. RESULTS: After the intervention, in the G25 and G50 groups, the thyroid stimulating hormone, triglyceride and low-density lipoprotein levels were notably less in contrast to those in the G0 group (P < 0.05). The rates of abdominal distension and SIBO in the G25 and G50 groups were notably lower in contrast to the G0 group (P = 0.043 and 0.040, respectively). The G50 group had a lower rate of spontaneous abortion and premature membrane rupture than the G0 group (P = 0.01 and 0.015, respectively). Before 11+ 2 weeks of gestation and at thyroid peroxidase antibodies levels ≥ 117 IU/mL, in contrast to the G0 group, the G50 group experienced a decreased rate of spontaneous abortion (P = 0.008). The G50 group had significantly higher newborn weight than the G0 group (P = 0.014), as well as a notably longer newborn length than the G0 and G25 groups (P = 0.005). CONCLUSIONS: For pregnant women with high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positive during the first half of pregnancy, supplementation with 50 µg levothyroxine was more effective in improving their blood lipid status and gastrointestinal symptoms, reducing the incidence of SIBO and premature rupture of membranes, and before 11+2 weeks, TPOAb ≥ 117 IU/mL proved more beneficial in mitigating the risk of spontaneous abortion.

Genome­wide analysis of the MYB gene family in pumpkin.

The MYB gene family exerts significant influence over various biological processes and stress responses in plants. Despite this, a comprehensive analysis of this gene family in pumpkin remains absent. In this study, the MYB genes of Cucurbita moschata were identified and clustered into 33 groups (C1-33), with members of each group being highly conserved in terms of their motif composition. Furthermore, the distribution of 175 CmoMYB genes across all 20 chromosomes was found to be non-uniform. Examination of the promoter regions of these genes revealed the presence of cis-acting elements associated with phytohormone responses and abiotic/biotic stress. Utilizing quantitative real-time polymerase chain reaction (qRT-PCR), the expression patterns of 13 selected CmoMYB genes were validated, particularly in response to exogenous phytohormone exposure and various abiotic stressors, including ABA, SA, MeJA, and drought treatments. Expression analysis in different tissues showed that CmoMYB genes are expressed at different levels in different tissues, suggesting that they are functionally divergent in regulating growth and abiotic stresses. These results provide a basis for future studies to characterize the function of the MYB gene family under abiotic stresses in pumpkins.

Bibliometric and visualization analysis of risk management in the doctor-patient relationship: A systematic quantitative literature review.

OBJECTIVES: This paper analyzed the research on risk management in the doctor-patient relationship (DPR) based on a systematic quantitative literature review approach using bibliometric software. It aims to uncover potential information about current research and predict future research hotspots and trends. METHODS: We conducted a comprehensive search for relevant publications in the Scopus database and the Web of Science Core Collection database from January 1, 2000 to December 31, 2023. We analyzed the data using CiteSpace 6.2.R2 and VOSviewer 1.6.19 software to examine the annual number of publications, countries/regions, journals, citations, authors, and keywords in the field. RESULTS: A total of 553 articles and reviews that met the criteria were included in this study. There is an overall upward trend in the number of publications issued; in terms of countries/regions, the United States and the United Kingdom are the largest contributors; Patient Education and Counseling is the most productive journal (17); Physician communication and patient adherence to treatment: a meta-analysis is the most cited article (1637); the field has not yet to form a stable and obvious core team; the analysis of high-frequency keywords revealed four main research directions: the causes of DPR risks, coping strategies, measurement tools, and research related to people prone to doctor-patient risk characteristics; the causes of DPR risks, coping strategies, measurement tools, and research related to people prone to doctor-patient risk characteristics; the keyword burst analysis revealed several shifts in the research hotspots for risk management in the DPR, suggesting that chronic disease management, is a future research direction for the continued development of risk management in the DPR. CONCLUSIONS: The visualization analysis of risk management literature in the DPR using CiteSpace and VOSviewer software provides insights into the current research status and highlights future research directions.