The value of intervention with radiotherapy after first-line chemo-immunotherapy in locally advanced or metastatic esophageal squamous cell carcinoma: A multi-center retrospective study.

Background: Chemotherapy plus immunotherapy has become the standard first-line treatment of advanced or metastatic esophageal squamous cell carcinoma (ESCC), but median duration of response is only 7.0-8.3 months and progression-free survival (PFS, ∼6 months) is still far from satisfactory. We aim to evaluate whether early involvement of radiotherapy might improve the treatment outcome if objective response to first-line chemo-immunotherapy was observed in locally advanced or metastatic ESCC. Methods: Patients were retrospectively collected from 3 institutions in China. Patients with histopathologically confirmed diagnoses of locally advanced or metastatic ESCC were identified, who objectively responded to first-line chemo-immunotherapy (complete or partial response, or stable disease) and also received radiotherapy of primary lesions with radiation dose of over 40 Gy, with or without radiotherapy of metastatic lesions before the first disease progression. Results: A total of 72 eligible patients were identified. With median follow-up duration of 14.6 (range, 7.1-34.8) months, median progression-free survival (PFS) and overall survival (OS) were 13.5 (95 % CI,10.4-NA) months and 31.8 (95 % CI, 23.0-NA) months, respectively. Median duration from initiation of chemo-immunotherapy to radiotherapy was 2.9 (range, 0-15.1) months. Besides lower tumor burden as a significant factor of better treatment outcome, radiation dose ≥ 50 Gy was associated with superior PFS, while OS might be mainly related to tumor response to the induction chemo-immunotherapy. A low incidence of Grade 3 or above treatment-related adverse events were observed (19 %), and no treatment-related death occurred. Conclusion: Our multi-center retrospective study showed survival benefit brought by early involvement of radiotherapy after first-line chemo-immunotherapy for patients with locally advanced or metastatic ESCC. However, further investigation is warranted in future prospective, controlled trials to assess the value of radio-immunotherapy in advanced or metastatic ESCC.

[Clinical characteristics of Ureaplasma urealyticum infection and colonization in extremely preterm infants]. / è¶ æ—©äº§å„¿è§£è„²è„²åŽŸä½“æ„ŸæŸ“åŠå®šæ¤çŠ¶æ€çš„ä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To investigate the clinical characteristics of Ureaplasma urealyticum (UU) infection and colonization in extremely preterm infants and its impact on the incidence of bronchopulmonary dysplasia (BPD). METHODS: A retrospective analysis was conducted on 258 extremely preterm infants who were admitted to the Department of Neonatology, Shenzhen Maternity and Child Healthcare Hospital, from September 2018 to September 2022. According to the results of UU nucleic acid testing and the evaluation criteria for UU infection and colonization, the subjects were divided into three groups: UU-negative group (155 infants), UU infection group (70 infants), and UU colonization group (33 infants). The three groups were compared in terms of general information and primary and secondary clinical outcomes. RESULTS: Compared with the UU-negative group, the UU infection group had significant increases in the incidence rate of BPD, total oxygen supply time, and the length of hospital stay (P<0.05), while there were no significant differences in the incidence rates of BPD and moderate/severe BPD between the UU colonization group and the UU-negative group (P>0.05). CONCLUSIONS: The impact of UU on the incidence of BPD in extremely preterm infants is associated with the pathogenic state of UU (i.e., infection or colonization), and there are significant increases in the incidence rate of BPD, total oxygen supply time, and the length of hospital stay in extremely preterm infants with UU infection. UU colonization is not associated with the incidence of BPD and moderate/severe BPD in extremely preterm infants.

Radiation-Induced Endothelial Ferroptosis Accelerates Atherosclerosis via the DDHD2-Mediated Nrf2/GPX4 Pathway.

This study sought to explore potential roles of endothelial ferroptosis in radiation-associated atherosclerosis (RAA) and molecular mechanisms behind this phenomenon. Here, an in vivo RAA mouse model was used and treated with ferroptosis inhibitors. We found that the RAA group had a higher plaque burden and a reduction in endothelial cells with increased lipid peroxidation compared to the control group, while ameliorated by liproxstatin-1. In vitro experiments further confirmed that radiation induced the occurrence of ferroptosis in human artery endothelial cells (HAECs). Then, proteomics analysis of HAECs identified domain-containing protein 2 (DDHD2) as a co-differentially expressed protein, which was enriched in the lipid metabolism pathway. In addition, the level of lipid peroxidation was elevated in DDHD2-knockdown HAECs. Mechanistically, a significant decrease in the protein and mRNA expression of glutathione peroxidase 4 (GPX4) was observed in HAECs following DDHD2 knockdown. Co-immunoprecipitation assays indicated a potential interaction between DDHD2 and nuclear factor erythroid 2-related factor 2 (Nrf2). The downregulation of Nrf2 protein was also detected in DDHD2-knockdown HAECs. In conclusion, our findings suggest that radiation-induced endothelial ferroptosis accelerates atherosclerosis, and DDHD2 is a potential regulatory protein in radiation-induced endothelial ferroptosis through the Nrf2/GPX4 pathway.

Salvage surgery and conversion surgery for patients with non-small cell lung cancer: A narrative review.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths. With the development of screening, patient selection and treatment strategies, patients' survival outcomes and living quality significantly improved. However, some patients still have local recurrence or residual tumors after receiving definitive therapies. Salvage surgery has been regarded as an effective option for recurrent or residual NSCLC, but its effectiveness remains undetermined. Furthermore, conversion surgery is a special type of salvage surgery for tumors converted from "initially unresectable" to "potentially resectable" status due to a favorable response to systemic treatments. Although conversion surgery is a promising curative procedure for advanced NSCLC, its concept and clinical value remain unfamiliar to clinicians. In this narrative review, we provided an overview of the safety and efficacy of salvage surgery, especially salvage surgery after sublobar resection in early-stage NSCLC. More importantly, we highlighted the concept and value of conversion surgery after systemic treatment in advanced NSCLC to gain some insights into its role in the treatment of lung cancer.

Nicotinate-curcumin improves NASH by inhibiting the AKR1B10/ACCα-mediated triglyceride synthesis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a prevalent chronic liver condition. However, the potential therapeutic benefits and underlying mechanism of nicotinate-curcumin (NC) in the treatment of NASH remain uncertain. METHODS: A rat model of NASH induced by a high-fat and high-fructose diet was treated with nicotinate-curcumin (NC, 20, 40 mg·kg- 1), curcumin (Cur, 40 mg·kg- 1) and metformin (Met, 50 mg·kg- 1) for a duration of 4 weeks. The interaction between NASH, Cur and Aldo-Keto reductase family 1 member B10 (AKR1B10) was filter and analyzed using network pharmacology. The interaction of Cur, NC and AKR1B10 was analyzed using molecular docking techniques, and the binding energy of Cur and NC with AKR1B10 was compared. HepG2 cells were induced by Ox-LDL (25 µg·ml- 1, 24 h) in high glucose medium. NC (20µM, 40µM), Cur (40µM) Met (150µM) and epalrestat (Epa, 75µM) were administered individually. The activities of ALT, AST, ALP and the levels of LDL, HDL, TG, TC and FFA in serum were quantified using a chemiluminescence assay. Based on the changes in the above indicators, score according to NAS standards. The activities of Acetyl-CoA and Malonyl-CoA were measured using an ELISA assay. And the expression and cellular localization of AKR1B10 and Acetyl-CoA carboxylase (ACCα) in HepG2 cells were detected by Western blotting and immunofluorescence. RESULTS: The results of the animal experiments demonstrated that NASH rat model induced by a high-fat and high-fructose diet exhibited pronounced dysfunction in liver function and lipid metabolism. Additionally, there was a significant increase in serum levels of FFA and TG, as well as elevated expression of AKR1B10 and ACCα, and heightened activity of Acetyl-CoA and Malonyl-CoA in liver tissue. The administration of NC showed to enhance liver function in rats with NASH, leading to reductions in ALT, AST and ALP levels, and decrease in blood lipid and significant inhibition of FFA and TG synthesis in the liver. Network pharmacological analysis identified AKR1B10 and ACCα as potential targets for NASH treatment. Molecular docking studies revealed that both Cur and NC are capable of binding to AKR1B10, with NC exhibiting a stronger binding energy to AKR1B10. Western blot analysis demonstrated an upregulation in the expression of AKR1B10 and ACCα in the liver tissue of NASH rats, accompanied by elevated Acetyl-CoA and Malonyl-CoA activity, and increased levels of FFA and TG. The results of the HepG2 cell experiments induced by Ox-LDL suggest that NC significantly inhibited the expression and co-localization of AKR1B10 and ACCα, while also reduced levels of TC and LDL-C and increased level of HDL-C. These effects are accompanied by a decrease in the activities of ACCα and Malonyl-CoA, and levels of FFA and TG. Furthermore, the impact of NC appears to be more pronounced compared to Cur. CONCLUSION: NC could effectively treat NASH and improve liver function and lipid metabolism disorder. The mechanism of NC is related to the inhibition of AKR1B10/ACCα pathway and FFA/TG synthesis of liver.

Comparison of the toxic effects of polystyrene and sulfonated polystyrene on wheat under cadmium stress.

With advances in plastic resource utilization technologies, polystyrene (PS) and sulfonated polystyrene (SPS) microplastics continue to be produced and retained in environmental media, potentially posing greater environmental risks. These plastics, due to their different physicochemical properties, may have different environmental impacts when compounded with other pollutants. The objective of this study was to investigate the combined toxic effects of PS and SPS on wheat using cadmium (Cd) as a background contaminant. The results demonstrated that Cd significantly impeded the normal growth of wheat by disrupting root development. Both PS and SPS exhibited hormesis at low concentrations and promoted wheat growth. Under combined toxicity, PS reduced oxidative stress and promoted the uptake of essential metal elements in wheat. Additionally, KEGG pathway analysis revealed that PS facilitated the repair of Cd-induced blockage of the TCA cycle and glutathione metabolism. However, high concentrations of SPS in combined toxicity not only enhanced oxidative stress and interfered with the uptake of essential metal elements, but also exacerbated the blocked TCA cycle and interfered with pyrimidine metabolism. These differences are related to the different stability (Zeta potential, Hydrodynamic particle size) of the two microplastics in the aquatic environment and their ability to carry heavy metal ions, especially Cd. The results of this study provide important insights into understanding the effects of microplastics on crops in the context of Cd contamination and their environmental and food safety implications.

Analysis of an Aqueous Extract from Turkish Galls Based on Multicomponent Qualitative and Quantitative Analysis Combined with Network Pharmacology and Chemometric Analysis.

The current quality control method for Turkish gall (TG) is limited to assessing total tannin or gallic acid (GA), which offers a basic level of quality control but does not fully capture the true quality of TG. Therefore, it is essential to establish a comprehensive method that utilizes multiple indicators to assess the intrinsic quality of TG. This research utilized UPLC-Q-TOF-MS/MS technology to qualitatively analyze the chemical composition of TG. Subsequently, the potential main active ingredients, targets, and pathways of TG in treating recurrent aphthous ulcers (RAU) were explored and analyzed using network pharmacology technology. Quantitative analysis of multicomponents by single marker (QAMS) was then employed to quantify the primary pharmacodynamic components in TG. Finally, chemometrics analysis was utilized to interpret the measured results and identify the markers of scavenging quality. The study identified 36 chemical components in TG, highlighting ellagic acid (EA), GA, and so on as key components in treating RAU. A method for simultaneously determining GA, EA, 1,2,3,6-tetra-O-galloyl-ß-D-glucose (TEGG) and 1,2,3,4,6-penta-O-galloyl-ß-D-glucose (PEGG) in TG was established. Statistical analysis revealed significant differences in the content of these 4 components across 14 batches of TG, with GA and PEGG identified as the primary contributors to the variations. This study determined a quality index for TG, providing a reference for quality evaluation and introducing a cost-effective and efficient quality control method. Furthermore, it addressed the challenge of developing new Chinese medicine by overcoming the lack of reference substances.

The Timing and Dose Effect of Acupuncture on Pregnancy Outcomes for Infertile Women Undergoing In Vitro Fertilization and Embryo Transfer: A Systematic Review and Meta-Analysis.

Background: Women undergoing in vitro fertilization and embryo transfer (IVF-ET) often utilize acupuncture to enhance pregnancy outcomes. Yet, the optimal timing for acupuncture sessions and the relationship between dosage and effect remain uncertain. Objectives: To investigate the impact of the timing and dosage of acupuncture on pregnancy outcomes, drawing on existing research. Methods: A comprehensive search of eight databases was conducted from their inception to January 14th, 2023, without restrictions on language. Only randomized controlled trials comparing acupuncture with either sham acupuncture or no adjuvant treatment were selected for inclusion. This meta-analysis assessed the efficacy of acupuncture in IVF-ET, analyzing the influence of varied timing and dosage on pregnancy outcomes. Subgroup analyses were undertaken to address any heterogeneity across the studies. Results: A total of 38 RCTs involving 5,991 participants were analyzed. In infertile women undergoing IVF fresh cycles, acupuncture performed during controlled ovarian hyperstimulation (COH) significantly increased the clinical pregnancy rate (CPR) (relative risk [RR] = 1.33, 95% confidence interval [CI]: 1.07-1.65, p = 0.01), whereas acupuncture administered either before COH or on the day of ET did not demonstrate reproductive benefits. Regarding frozen cycles, acupuncture before freeze-thaw embryo transfer (FET) significantly enhanced the CPR (RR = 1.71, 95% CI: 1.36-2.16, p < 0.00001) and live birth rate (LBR) (RR = 2.40, 95% CI: 1.20-4.79, p = 0.01). Improvements in CPR were observed across all dosage groups, but only the high-dosage group showed a significant increase in LBR (RR = 1.75, 95% CI: 1.05-2.92, p = 0.03). Conclusions: Timing and dosage of acupuncture are crucial factors affecting pregnancy outcomes in IVF-ET. For women undergoing IVF fresh cycles, acupuncture during COH yielded more significant reproductive benefits. In addition, acupuncture before freeze-thaw embryo transfer (FET) was associated with improved pregnancy outcomes in frozen cycles. Furthermore, higher dosages of acupuncture were linked to more favorable outcomes.

Cost-effectiveness of additional serplulimab to chemotherapy in metastatic squamous non-small cell lung cancer patients.

Objective: To estimate the cost-effectiveness of adding serplulimab to chemotherapy for metastatic squamous non-small cell lung cancer (NSCLC) patients in a first-line setting from a Chinese perspective. Methods: A three-health state partitioned survival model was constructed to simulate disease development. The clinical data used in the model were derived from the ASTRUM-004 clinical trial. Only direct medical costs were included, and the utilities were derived from published literature. The quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were employed to evaluate health outcomes. Additionally, a sensitivity analysis was performed to verify the robustness of the results. Results: Compared with chemotherapy alone, the addition of serplulimab resulted in an increase of 0.63 QALYs with an incremental cost of $5,372.73, leading to an ICER of $8,528.14 per QALY. This ICER was significantly lower than 3 times China's per capita GDP. The one-way sensitivity analysis suggested that the utility of PFS was the most sensitive factor on ICERs, followed by the price of serplulimab. Conclusion: The combination of serplulimab and chemotherapy has been shown to be a cost-effective initial treatment option for patients with metastatic squamous NSCLC with the commonly accepted willingness-to-pay threshold of 3 times the GDP per capita per QALY in China.

A real-world analysis of stereotactic body radiotherapy combined with immunotherapy in advanced or recurrent non-small cell lung cancer (NSCLC): A single-center experience.

Background: We aimed to assess the value of stereotactic body radiotherapy (SBRT) delivered under the situation of controlled or progressed disease during ICI therapy in advanced or recurrent NSCLC. Methods: We retrospectively collected patients with advanced or recurrent NSCLC who received SBRT concurrently with ICI in our institution between January 2017 and December 2021. Patients were divided into two groups, including those for whom SBRT was delivered initially or to the residual tumors during the first- or later-line ICI treatment (Group 1), and those for whom SBRT was given to the progressed tumors irrespective of first- or later-line ICI treatment (Group 2). Results: A total of 144 patients were included. With median follow-up duration of 25.6 (range: 3.6 to 56.2) months, median progression-free survival (PFS) was 13.7 (95 % CI: 10.4 to 17.1) months and median overall survival (OS) was 52.8 [95 % CI: 30.6 to not available (NA)] months. In Group 1 (n = 78), median PFS was 17.9 (95 % CI: 14.5 to 29.8) months while median OS was not reached and 5-year OS rate was 61.2 %. In Group 2 (n = 66), median PFS was 8.0 (95 % CI: 6.0 to 13.1) months and median OS was 30.6 (95 % CI: 21.5 to NA) months. Conclusions: SBRT combined with ICI demonstrated favorable survival for advanced or recurrent NSCLC, delivered in a controlled-disease situation as well as to progressed diseases with salvage-intent. Future prospective studies are warranted to investigate the optimal SBRT dose regimen and appropriate combination strategy to synergize ICI.

Protein painting for structural and binding site analysis via intracellular lysine reactivity profiling with o-phthalaldehyde.

The three-dimensional structure and the molecular interaction of proteins determine their roles in many cellular processes. Chemical protein painting with protein mass spectrometry can identify changes in structural conformations and molecular interactions of proteins including their binding sites. Nevertheless, most current protein painting techniques identify protein targets and binding sites of drugs in vitro using a cell lysate or purified protein. Here, we tested 11 membrane-permeable lysine-reactive chemical probes for intracellular covalent labeling of endogenous proteins, which reveals ortho-phthalaldehyde (OPA) as the most reactive probe in the intracellular environment. An MS workflow and a new data analysis strategy termed RAPID (Reactive Amino acid Profiling by Inverse Detection) was developed to enhance detection sensitivity. RAPID with OPA successfully identified structural changes induced by the allosteric drug TEPP-46 on its target protein PKM2 and was applied to profile the conformation change of the proteome occurring in cells during thermal denaturation. The application of RAPID-OPA on cells treated with geldanamycin, selumetinib, and staurosporine successfully revealed their binding sites on target proteins. Thus, RAPID-OPA for cellular protein painting enables the identification of ligand-binding sites and detection of protein structural changes occurring in cells.

Early changes in cardiac troponin T and NT-proBNP levels in neonates receiving ECMO support: a single-center experience.

OBJECTIVE: This study aimed to examine the changes in absolute value and decline rate of early serum cardiac troponin T (cTnT) and N-terminal pro b-type natriuretic peptide (NT-proBNP) in neonates who received veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) support therapy within the first week of life. METHODS: We retrospectively collected clinical data and laboratory test results of 18 neonates who underwent V-A ECMO support within one week of birth, from July 2021 to June 2023, using the electronic medical record system. These patients were categorized into survival and death groups. Comparative analyses of the absolute values and decline rates of cTnT and NT-proBNP were made between the groups at baseline, and at 24, 48, and 72 h post-ECMO initiation. RESULTS: Out of the 18 neonates, 12 survived (survival rate: 66.7%), while 6 succumbed. The survival group exhibited significantly lower absolute values of cTnT and NT-proBNP than the death group, and their decline rates were significantly higher. Notably, all neonates without an early decline in cTnT and NT-proBNP levels were in the death group. CONCLUSION: The early changes in the absolute value and decline rate of serum cTnT and NT-proBNP in neonates undergoing V-A ECMO may serve as predictors of their prognosis.

Comparative efficacy and safety between endoscopic submucosal dissection, surgery and definitive chemoradiotherapy in patients with cT1N0M0 esophageal cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) and surgical resection are the standard of care for cT1N0M0 esophageal cancer (EC), whereas definitive chemoradiotherapy (d-CRT) is a treatment option. Nevertheless, the comparative efficiency and safety of ESD, surgery and d-CRT for cT1N0M0 EC remain unclear. AIM: To compare the efficiency and safety of ESD, surgery and d-CRT for cT1N0M0 EC. METHODS: We retrospectively analyzed the hospitalized data of a total of 472 consecutive patients with cT1N0M0 EC treated at Sun Yat-sen University Cancer center between 2017-2019 and followed up until October 30th, 2022. We analyzed demographic, medical recorded, histopathologic characteristics, imaging and endoscopic, and follow-up data. The Kaplan-Meier method and Cox proportional hazards modeling were used to analyze the difference of survival outcome by treatments. Inverse probability of treatment weighting (IPTW) was used to minimize potential confounding factors. RESULTS: We retrospectively analyzed patients who underwent ESD (n = 99) or surgery (n = 220) or d-CRT (n = 16) at the Sun Yat-sen University Cancer Center from 2017 to 2019. The median follow-up time for the ESD group, the surgery group, and the d-CRT group was 42.0 mo (95%CI: 35.0-60.2), 45.0 mo (95%CI: 34.0-61.75) and 32.5 mo (95%CI: 28.3-40.0), respectively. After adjusting for background factors using IPTW, the highest 3-year overall survival (OS) rate and 3-year recurrence-free survival (RFS) rate were observed in the ESD group (3-year OS: 99.7% and 94.7% and 79.1%; and 3-year RFS: 98.3%, 87.4% and 79.1%, in the ESD, surgical, and d-CRT groups, respectively). There was no difference of severe complications occurring between the three groups (P ≥ 0.05). Multivariate analysis showed that treatment method, histology and depth of infiltration were independently associated with OS and RFS. CONCLUSION: For cT1N0M0 EC, ESD had better long-term survival and lower hospitalization costs than those who underwent d-CRT and surgery, with a similar rate of severe complications occurring.

Cancer diagnosis and treatment platform based on manganese-based nanomaterials.

Cancer is a leading cause of death worldwide, and the development of new diagnostic and treatment methods is crucial. Manganese-based nanomaterials (MnNMs) have emerged as a focal point in the field of cancer diagnosis and treatment due to their multifunctional properties. These nanomaterials have been extensively explored as contrast agents for various imaging technologies such as magnetic resonance imaging (MRI), photoacoustic imaging (PAI), and near-infrared fluorescence imaging (NIR-FL). The use of these nanomaterials has significantly enhanced the contrast for precise tumor detection and localization. Moreover, MnNMs have shown responsiveness to the tumor microenvironment (TME), enabling innovative approaches to cancer treatment. This review provides an overview of the latest developments of MnNMs and their potential applications in tumor diagnosis and therapy. Finally, potential challenges and prospects of MnNMs in clinical applications are discussed. We believe that this review would serve as a valuable resource for guiding further research on the application of manganese nanomaterials in cancer diagnosis and treatment, addressing the current limitations, and proposing future research directions.

Improvement of Prediction Performance for Radiation Pneumonitis by Using 3-Dimensional Dosiomic Features.

INTRODUCTION: Patients with early non-small-cell lung cancer (NSCLC) have a relatively long survival time after stereotactic body radiation therapy (SBRT). Predicting radiation-induced pneumonia (RP) has important clinical and social implications for improving the quality of life of such patients. This study developed an RP prediction model by using 3-dimensional (3D) dosiomic features. The model can be used to guide radiation therapy to reduce toxicity. METHODS: Radiomic features were extracted from pre-treatment CT, dose-volume histogram (DVH) parameters and dosiomic features were extracted from the 3D dose distribution of 140 lung cancer patients. Four predictive models: (1) CT; (2) CT + DVH; (3) CT + Rtdose; and (4) Hybrid, CT + DVH + Rtdose, were trained to predict symptomatic RP by extremely randomized trees. Accuracy, sensitivity, specificity, and area under the receiver operator characteristic curve were evaluated. RESULT: Results showed that the fraction regimen was correlated with symptomatic RP (P < .001). The proposed model achieved promising prediction results. The performance metrics for CT, CT + DVH, CT + Rtdose, and Hybrid were as follows: accuracy: 0.786, 0.821, 0.821, and 0.857; sensitivity: 0.625, 1, 0.875, and 1; specificity: 0.8, 0.565, 0.5, and 0.875; and area under the receiver operator characteristic curve: 0.791, 0.809, 0.907, and 0.920, respectively. CONCLUSION: Dosiomic features can improve the performance of the predictive model for symptomatic RP compared with that obtained with the CT + DVH model. The model proposed in this study can help radiation oncologists individually predict the incidence rate of RP.

Complete mitochondrial genome sequence of Butyriboletus hainanensis (Boletales, Basidiomycota).

Butyriboletus hainanensis, a macrofungus belonging to the Boletaceae family, is named after its collection location on Hainan Island, China. However, little is known about its mitochondrial genome and its phylogenetic relationship with other boletes. In this study, we utilized next-generation sequencing technology to sequence the mitochondrial genome of Bu. hainanensis. Our findings revealed that the mitochondrial genome of this species is presumably a circular DNA molecule spanning 36,592 bp. It consists of 15 protein-coding genes, 27 transfer RNA genes, and two ribosomal RNA genes. The base composition of the mitochondrial genome is as follows: A (36.64%), C (12.22%), G (11.73%), and T (39.41%), with a GC content of 23.95%. Additionally, a phylogenetic tree was constructed based on 22 mitochondrial genomes, which provided valuable insights into the phylogenetic relationships of Bu. hainanensis with other boletes for the first time.

Purification, structural characteristics and anti-atherosclerosis activity of a novel green tea polysaccharide.

A new homogeneous polysaccharide (TPS3A) was isolated and purified from Tianzhu Xianyue fried green tea by DEAE-52 cellulose and Sephacryl S-500 column chromatography. Structural characterization indicated that TPS3A mainly consisted of arabinose, galactose, galacturonic acid and rhamnose in a molar ratio of 5.84: 4.15: 2.06: 1, with an average molecular weight of 1.596 × 104 kDa. The structure of TPS3A was characterized as a repeating unit consisting of 1,3-Galp, 1,4-Galp, 1,3,6-Galp, 1,3-Araf, 1,5-Araf, 1,2,4-Rhap and 1-GalpA, with two branches on the C6 of 1,3,6-Galp and C2 of 1,2,4-Rhap, respectively. To investigate the preventive effects of TPS3A on atherosclerosis, TPS3A was administered orally to ApoE-deficient (ApoE-/-) mice. Results revealed that TPS3A intervention could effectively delay the atherosclerotic plaque progression, modulate dyslipidemia, and reduce the transformation of vascular smooth muscle cells (VSMCs) from contractile phenotype to synthetic phenotype by activating the expression of contractile marker alpha-smooth muscle actin (α-SMA) and inhibiting the expression of synthetic marker osteopontin (OPN) in high-fat diet-induced ApoE-/- mice. Our findings suggested that TPS3A markedly alleviated atherosclerosis by regulating dyslipidemia and phenotypic transition of VSMCs, and might be used as a novel functional ingredient to promote cardiovascular health.

Endoplasmic reticulum stress is upregulated in inflammatory bowel disease and contributed TLR2 pathway-mediated inflammatory response.

OBJECTIVE: Endoplasmic reticulum stress (ERS) and Toll-like receptor 2 (TLR2) signaling play an important role in inflammatory bowel disease (IBD); however, the link between TLR2 and ERS in IBD is unclear. This study investigated whether Thapsigargin (TG) -induced ER protein expression levels contributed to TLR2-mediated inflammatory response. METHODS: The THP-1 cells were treated with TLR2 agonist (Pam3CSK4), ERS inducer Thapsigargin (TG) or inhibitor (TUDCA). The mRNA expressions of TLR1-TLR10 were detected by qPCR. The production and secretion of inflammatory factors were detected by PCR and ELISA. Immunohistochemistry was used to detect the expressions of GRP78 and TLR2 in the intestinal mucosa of patients with Crohn's disease (CD). The IBD mouse model was established by TNBS in the modeling group. ERS inhibitor (TUDCA) was used in the treatment group. RESULTS: The expression of TLRs was detected via polymerase chain reaction (PCR) in THP-1 cells treated by ERS agonist Thapsigargin (TG). According to the findings, TG could promote TLR2 and TLR5 expression. Subsequently, in TLR2 agonist Pam3CSK4 induced THP-1 cells, TG could lead to increased expression of the inflammatory factors such as TNF-α, IL-1ß and IL-8, and ERS inhibitor (TUDCA) could block this effect. However, Pam3CSK4 did not significantly impact the GRP78 and CHOP expression. Based upon the immunohistochemical results, TLR2 and GRP78 expression were significantly increased in the intestinal mucosa of patients with Crohn's disease (CD). For in vivo experiments, TUDCA displayed the ability to inhibit intestinal mucosal inflammation and reduce GRP78 and TLR2 proteins. CONCLUSIONS: ERS and TLR2 is upregulated in inflammatory bowel disease, ERS may promote TLR2 pathway-mediated inflammatory response. Moreover, ERS and TLR2 signaling could be novel therapeutic targets for IBD.

Nickel-Catalyzed Three-Component Alkylarylation of Alkenyl N-Heteroarenes.

A nickel-catalyzed three-component alkylarylation of alkenyl N-heteroarenes with α-bromocarboxylates and aryl boronic acids is reported. The protocol provides a new method to access a variety of N-heteroarene substituted diarylalkanes in moderate to good yields. It features mild reaction conditions, cheap nickel catalyst, readily available substrates, and broad substrate scope.

Polypharmacy, potentially inappropriate medications, and drug-drug interactions in older COVID-19 inpatients.

OBJECTIVES: The purpose of this study was to assess the impact of polypharmacy, potentially inappropriate medications, and drug-drug interactions on in-hospital mortality in older COVID-19 inpatients. METHODS: A cross-sectional study was conducted using electronic medical data from a tertiary hospital in Chengdu from December 2022 to January 2023. The 2019 AGS/Beers criteria was used to evaluate the potentially inappropriate mediation (PIM) status of older COVID-19 inpatients (age ≥ 65 years), the drug-drug interactions were evaluated on Medscape, and multivariate logistic regression was used to identify the risk factors associated with in-hospital mortality. RESULTS: A total of 206 older COVID-19 inpatients were included in the study. The mean number of drugs per day was 13.04. The prevalence of PIM use based on the 2019 AGS Beers Criteria was 66.99%. The prevalence of drug-drug interactions was 61.65%. Logistic regression demonstrated that age ≥ 80 (OR: 10.321, 95% CI: 1.649, 64.579, P = 0.013), renal insufficiency (OR: 4.740, 95% CI: 1.366, 16.447, P = 0.014), long-term hospitalization (OR: 6.637, 95% CI: 1.030, 42.779, P = 0.046), severe pneumonia (OR: 50.230, 95% CI: 5.180, 487.041, P = 0.001) were influencing factors associated with in-hospital mortality in older COVID-19 inpatients. CONCLUSIONS: The polypharmacy, potentially inappropriate medications, and drug-drug interactions were seen in many older COVID-19 inpatients.