Evaluation of the therapeutic effects of Photodynamic Therapy in vulvar lichen sclerosus and impact on patient quality of life and sexual funtion.

BACKGROUND: Vulvar lichen sclerosus (VLS) is often associated with irritable symptoms of itching, burning pain and can lead to scarring, architectural changes and sexual dysfunction as well as a decline in quality of life.The etiology of the disease is unknown. This study sought to assess the therapeutic effects of Photodynamic Therapy (PDT) in VLS, and improvment of patient quality of life and sexual funtion. METHODS: From January 2022 to April 2023, a total of 65 patients with vulvar sclerosi (VLS) were treated with PDT in our hospital. All 65 patients were divided into two groups: early-stage group and late-stage group. The Cattaneo scoring method, the Dermatology Life Quality Index (DLQI) and the Female Sexual Function Index (FSFI) scores were used to evaluate the clinical effectiveness of the treatment on patients' symptoms and clincal signs, quality of life as well as sexual function before and at 6-month after treatment. RESULTS: The total effective rate of early-stage patients was significantly greater than that of late-stage patients at 6-month after PDT treatment (90.91% [40/44] vs 76.19% [16/21], p <0.05). At 6-month follow-up, the symptoms and clinical signs of patients in early-stage group were significantly improved compared with baseline, the average scores of itching, skin elasticity, whitening and lesion range were significantly lower than the scores before treatment (p <0.05). In late-stage group, The decrease in scores of itching, whitening and lesion range at the 6-months follow-up is significant(p <0.05), but skin elasticity (p=0.0625). On post-treatment follow-up examination, FSFI score was seen to have significantly improved in early-stage patients(from a median score of 17.45 to 21.1, p<0.05); DLQI also significantly improved after treatment (from a median score of 7 to 4, p<0.05). In late stage patients, The DLQI score improved significantly after treatment (from a median score of 18 to 15, p<0.05). However, the improvement in sexual function is not statistically significant (pre-treatment: median=10.55, post-treatment: median=10, p=0.1865). CONCLUSION: Photodynamic therapy can effectively improve most symptoms and clinical signs, as well as quality of life of patients with VLS, especially for earlly stage patients. Moreover, improvement in sexual function is observed in early stage patients after PDT treatment. This study suggests that early and timely PDT treatment are recommended to achieve better results.

Efficacy and Safety of Anti-Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Antibodies Plus Chemotherapy as First-Line Treatment for NSCLC in the People's Republic of China: a Systematic Review and Meta-Analysis.

Introduction: The available approved anticancer drugs for Chinese patients are relatively limited because of China's low participation rate in international clinical trials. Therefore, a focus on approved anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) drugs in China is needed. This study aims to assess the heterogeneity of anti-PD-1/PD-L1 antibodies manufactured in China (domestic PD-1/PD-L1) and overseas (imported PD-1/PD-L1) when combined with chemotherapy as the first-line treatment of NSCLC. Methods: A systematic search was performed using PubMed, EMBASE, and Cochrane Library of publications up to July 13, 2023. Meta-analysis was applied to compare the efficacy and safety profile between anti-PD-1/PD-L1 antibodies plus chemotherapy (PD-1/PD-L1+Chemo) and chemotherapy alone using STATA software. Pooled hazard ratios for progression-free survival and overall survival, odds ratios for objective response rate, and incidence rate of grade greater than or equal to three treatment-related adverse events with 95% confidence intervals were calculated in the domestic group and imported group by a random-effects model, and the heterogeneity between the two estimates was assessed. Results: There were 14 eligible clinical studies with a total of 3951 patients involved in this analysis, including eight studies of domestic PD-1/PD-L1+Chemo and six studies of imported PD-1/PD-L1+Chemo. The study revealed that there was no significant difference between domestic and imported PD-1/PD-L1+Chemo in overall survival (p = 0.80), progression-free survival (p = 0.53), and incidence rate of grade greater than or equal to three treatment-related adverse events (p = 0.10). Nevertheless, the objective response rate of imported PD-1/PD-L1+Chemo was significantly higher than that of domestic PD-1/PD-L1+Chemo (p = 0.03). Conclusions: Domestic anti-PD-1/PD-L1 antibodies plus chemotherapy were found to have comparable efficacy and safety to those combined with imported anti-PD-1/PD-L1 antibodies based on current evidence.

Impact of stress hyperglycemia ratio on mortality in patients with cardiac arrest: insight from American MIMIC-IV database.

Background: Stress hyperglycemia ratio (SHR) has shown a predominant correlation with transient adverse events in critically ill patients. However, there remains a gap in comprehensive research regarding the association between SHR and mortality among patients experiencing cardiac arrest and admitted to the intensive care unit (ICU). Methods: A total of 535 patients with their initial ICU admission suffered cardiac arrest, according to the American Medical Information Mart for Intensive Care (MIMIC)-IV database. Patients were stratified into four categories based on quantiles of SHR. Multivariable Cox regression models were used to evaluate the association SHR and mortality. The association between SHR and mortality was assessed using multivariable Cox regression models. Subgroup analyses were conducted to determine whether SHR influenced ICU, 1-year, and long-term all-cause mortality in subgroups stratified according to diabetes status. Results: Patients with higher SHR, when compared to the reference quartile 1 group, exhibited a greater risk of ICU mortality (adjusted hazard ratio [aHR] = 3.029; 95% CI: 1.802-5.090), 1-year mortality (aHR = 3.057; 95% CI: 1.885-4.958), and long-term mortality (aHR = 3.183; 95% CI: 2.020-5.015). This association was particularly noteworthy among patients without diabetes, as indicated by subgroup analysis. Conclusion: Elevated SHR was notably associated with heightened risks of ICU, 1-year, and long-term all-cause mortality among cardiac arrest patients. These findings underscore the importance of considering SHR as a potential prognostic factor in the critical care management of cardiac arrest patients, warranting further investigation and clinical attention.

Identification and diagnostic potential of hsa_circ_101303 in colorectal cancer: unraveling a regulatory network.

BACKGROUND: The role of novel circular RNAs (circRNAs) in colorectal cancer (CRC) remains to be determined. This study aimed to identify a novel circRNA involved in CRC pathogenesis, assess its diagnostic value, and construct a regulatory network. METHODS: Differential expression analysis was conducted using circRNA datasets to screen for differentially expressed circRNAs. The expression of selected circRNAs was validated in external datasets and clinical samples. Diagnostic value of plasma circRNA levels in CRC was assessed. A competing endogenous RNA (ceRNA) network was constructed for the circRNA using TCGA dataset. RESULTS: Analysis of datasets revealed that hsa_circ_101303 was significantly overexpressed in CRC tissues compared to normal tissues. The upregulation of hsa_circ_101303 in CRC tissues was further confirmed through the GSE138589 dataset and clinical samples. High expression of hsa_circ_101303 was associated with advanced N stage, M stage, and tumor stage in CRC. Plasma levels of hsa_circ_101303 were markedly elevated in CRC patients and exhibited moderate diagnostic ability for CRC (AUC = 0.738). The host gene of hsa_circ_101303 was also found to be related to the TNM stage of CRC. Nine miRNAs were identified as target miRNAs for hsa_circ_101303, and 27 genes were identified as targets of these miRNAs. Subsequently, a ceRNA network for hsa_circ_101303 was constructed to illustrate the interactions between the nine miRNAs and 27 genes. CONCLUSIONS: The study identifies hsa_circ_101303 as a highly expressed circRNA in CRC, which is associated with the progression of the disease. Plasma levels of hsa_circ_101303 show promising diagnostic potential for CRC. The ceRNA network for hsa_circ_101303 provides valuable insights into the regulatory mechanisms underlying CRC.

1,5-Hydrogen atom transfer of α-iminyl radical cations: a new platform for relay annulation for pyridine derivatives and axially chiral heterobiaryls.

The exploitation of new reactive species and novel transformation modes for their synthetic applications have significantly promoted the development of synthetic organic methodology, drug discovery, and advanced functional materials. α-Iminyl radical cations, a class of distonic ions, exhibit great synthetic potential for the synthesis of valuable molecules. For their generation, radical conjugate addition to α,ß-unsaturated iminium ions represents a concise yet highly challenging route, because the in situ generated species are short-lived and highly reactive and they have a high tendency to cause radical elimination (ß-scission) to regenerate the more stable iminium ions. Herein, we report a new transformation mode of the α-iminyl radical cation, that is to say, 1,5-hydrogen atom transfer (1,5-HAT). Such a strategy can generate a species bearing multiple reactive sites, which serves as a platform to realize (asymmetric) relay annulations. The present iron/secondary amine synergistic catalysis causes a modular assembly of a broad spectrum of new structurally fused pyridines including axially chiral heterobiaryls, and exhibits good functional group tolerance. A series of mechanistic experiments support the α-iminyl radical cation-induced 1,5-HAT, and the formation of several radical species in the relay annulations. Various synthetic transformations of the reaction products demonstrate the usefulness of this relay annulation protocol for the synthesis of significant molecules.

Complete mitochondrial genome data and phylogenetic analysis of Papilio macilentus Janson, 1877 (Lepidoptera: Papilionoidea: Papilionidae).

In the present study, the complete mitochondrial genome (mitogenome) of the Papilio macilentus (Lepidoptera: Papilionoidea: Papilionidae) was sequenced by next-generation sequencing method. The mitochondrial genome is a circular DNA molecule of 15,264 bp in size with 80.7% AT content, including 37 genes (13 protein-coding genes, 2 rRNA genes, and 22 tRNA genes), and a long non-coding region (Control region). All protein-coding genes are initiated by ATN codons, and terminated with TAA, TAG, or single T. All tRNAs can be folded into common clover leaf secondary structure, except trn-S1. Phylogenetic analyses based on 13 protein-coding genes and 2 rRNA genes using maximum likelihood and Bayesian inference confirmed that P. macilentus and Papilio memnon are clustered into a clade, and revealed the relationships between Papilionini, Troidini, Teinopaippini and Leptocircini.

Targeting OXCT1-mediated ketone metabolism reprograms macrophages to promote antitumor immunity via CD8+ T cells in hepatocellular carcinoma.

BACKGROUND & AIMS: The liver is the main organ of ketogenesis, while ketones are mainly metabolized in peripheral tissues via the critical enzyme OXCT1. We previously found that ketolysis is reactivated in hepatocellular carcinoma (HCC) cells through OXCT1 expression to promote tumor progression; however, whether OXCT1 regulates antitumor immunity remains unclear. METHODS: To investigate the expression pattern of OXCT1 in hepatocellular carcinoma in vivo, we conducted multiplex immunohistochemistry (mIHC) experiments on human HCC specimens. To explore the role of OXCT1 in mouse hepatocellular carcinoma tumor-associated macrophages (TAMs), we generated LysMcreOXCT1f/f (OXCT1 conditional knockout in macrophages) mice. RESULTS: Here, we found that inhibiting OXCT1 expression in tumor-associated macrophages reduced CD8+ T-cell exhaustion through the succinate-H3K4me3-Arg1 axis. Initially, we found that OXCT1 was highly expressed in liver macrophages under steady state and that OXCT expression was further increased in TAMs. OXCT1 deficiency in macrophages suppressed tumor growth by reprogramming TAMs toward an antitumor phenotype, reducing CD8+ T-cell exhaustion and increasing CD8+ T-cell cytotoxicity. Mechanistically, high OXCT1 expression induced the accumulation of succinate, a byproduct of ketolysis, in TAMs, which promoted Arg1 transcription by increasing the H3K4 trimethylation (H3K4me3) level in the Arg1 promoter. In addition, Pimozide, an inhibitor of OXCT1, suppressed Arg1 expression as well as TAM polarization toward the protumor phenotype, leading to decreasing CD8+ T-cell exhaustion and deceleration of tumor growth. Finally, high expression of OXCT1 in macrophages was positively associated with poor survival in HCC patients. CONCLUSIONS: In conclusion, our results demonstrate that OXCT1 epigenetically suppresses antitumor immunity, suggesting that suppressing OXCT1 activity in TAMs is an effective approach for treating liver cancer. IMPACT AND IMPLICATIONS: The intricate metabolism of liver macrophages plays a critical role in shaping HCC progression and immune modulation. Targeting macrophage metabolism to counteract immune suppression presents a promising avenue for HCC. Here, we found that ketogenesis gene OXCT1 was highly expressed in tumor-associated macrophages and promoted tumor growth by reprogramming TAMs toward a protumor phenotype. And the strategic pharmacological intervention or genetic downregulation of OXCT1 in TAMs enhances the antitumor immunity and decelerated tumor growth. Our results suggest that suppressing OXCT1 activity in TAMs is an effective approach for treating liver cancer.

Mining Real-World Big Data to Characterize Adverse Drug Reaction Quantitatively: Mixed Methods Study.

BACKGROUND: Adverse drug reactions (ADRs), which are the phenotypic manifestations of clinical drug toxicity in humans, are a major concern in precision clinical medicine. A comprehensive evaluation of ADRs is helpful for unbiased supervision of marketed drugs and for discovering new drugs with high success rates. OBJECTIVE: In current practice, drug safety evaluation is often oversimplified to the occurrence or nonoccurrence of ADRs. Given the limitations of current qualitative methods, there is an urgent need for a quantitative evaluation model to improve pharmacovigilance and the accurate assessment of drug safety. METHODS: In this study, we developed a mathematical model, namely the Adverse Drug Reaction Classification System (ADReCS) severity-grading model, for the quantitative characterization of ADR severity, a crucial feature for evaluating the impact of ADRs on human health. The model was constructed by mining millions of real-world historical adverse drug event reports. A new parameter called Severity_score was introduced to measure the severity of ADRs, and upper and lower score boundaries were determined for 5 severity grades. RESULTS: The ADReCS severity-grading model exhibited excellent consistency (99.22%) with the expert-grading system, the Common Terminology Criteria for Adverse Events. Hence, we graded the severity of 6277 standard ADRs for 129,407 drug-ADR pairs. Moreover, we calculated the occurrence rates of 6272 distinct ADRs for 127,763 drug-ADR pairs in large patient populations by mining real-world medication prescriptions. With the quantitative features, we demonstrated example applications in systematically elucidating ADR mechanisms and thereby discovered a list of drugs with improper dosages. CONCLUSIONS: In summary, this study represents the first comprehensive determination of both ADR severity grades and ADR frequencies. This endeavor establishes a strong foundation for future artificial intelligence applications in discovering new drugs with high efficacy and low toxicity. It also heralds a paradigm shift in clinical toxicity research, moving from qualitative description to quantitative evaluation.

[Correlation between intestinal toxicity and composition changes of toxic parts from Euphorbia ebracteolata before and after Terminalia chebula soup processing].

This study aims to explore the correlation between intestinal toxicity and composition changes of Euphorbia ebracteolata before and after Terminalia chebula soup(TCS) processing. Intragastric administration was performed on the whole animal model. By using fecal water content, inflammatory causes, and pathological damage of different parts of the intestinal tract of mice as indexes, the differences in intestinal toxicity of dichloromethane extraction of raw E. ebracteolata(REDE), dichloromethane extraction of TCS, and dichloromethane extraction of E. ebracteolata after simulated TCS processing(STREDE) were compared, so as to investigate the effect of TCS processing on the intestinal toxicity of E. ebracteolata. At the same time, the component databases of E. ebracteolata and T. chebula were constructed, and the composition changes of diterpenoids, tannins, and phenolic acids in the three extracted parts were analyzed by HPLC-TOF-MS. HPLC was used to compare the content of four diterpenoids including ent-11α-hydroxyabicta-8(14), 13(15)-dien-16, 12-olide(HAO), jolkinolide B(JNB), fischeria A(FA), and jolkinolide E(JNE) in the E. ebracteolata before and after processing and the residue of container wall after processing, so as to investigate the effect of TCS processing on the content and structure of the diterpenoids. The results showed that the REDE group could significantly increase the fecal water content and the release levels of TNF-α and IL-1ß from each intestinal segment, and intestinal tissue damage was accompanied by significant infiltration of inflammatory cells. However, compared with the REDE group, the intestinal tissue damage in the STREDE group was alleviated, and the infiltration of inflammatory cells decreased. The intestinal toxicity significantly decreased. Mass spectrometry analysis showed that there was no significant difference in the content of diterpenoids of REDE before and after simulated TCS processing, but a large number of tannins and phenolic acids were added. The results of HPLC showed that the content of four diterpenoids of E. ebracteo-lata decreased to varying degrees after TCS processing, ranging from-0.35% to-19.74%, and the decreased part mainly remained in the container wall, indicating that the structure of toxic diterpenoids of E. ebracteolata was not changed after TCS processing. The antagonistic effect of tannic and phenolic acids in the TCS may be the main reason for the reduced intestinal toxicity of E. ebracteolata after TCS processing. The TCS processing for E. ebracteolata is scientific.

[Content of secondary metabolites and antioxidant activities of Lonicera japonica flowers at different developmental stages from Shandong province].

This study established an ultrasound-assisted extraction-high performance liquid chromatography method for simulta-neously determinining the content of 11 bioactive compounds including iridoids, phenolic acids, and flavonoids in Lonicera japonica flowers. The flowers at six stages from the rice bud stage(ML) to the golden flower stage(JH) of L. japonica varieties 'Sijuhua' and 'Beihua No.1' in two planting bases in Shandong province were collected. The established method was employed to determine the content of 11 target compounds, on the basis of which the dynamics of active components in L. japonica sampels during different development stages was investigated. The correlation analysis was carried out to reveal the correlations of the content of iridoids, phenolic acids, and flavonoids. Furthermore, the antioxidant activities of samples at different developmental stages were determined, and the relationship between antioxidant activity and chemical components was analyzed by the correlation analysis. The results showed that the total content of the 11 components in 'Sijihua' changed in a "W" pattern from the ML to JH, being the highest at the ML and the second at the slight white stage(EB). The total content of 11 compounds in 'Beihua No.1' was the highest at the ML and decreased gra-dually from the ML to JH. The samples of 'Sijihua' had higher content of iridoids and lower content of phenolic acids than those of 'Beihua No.1'. The content of flavonoids and phenolic acids showed a positive correlation(R~2=0.90, P<0.05) in 'Sijihua' but no obvious correlation in 'Beihua No.1'. The antioxidant activity and phenolic acid content showed positive correlations, with the determination coefficients(R~2) of 0.84(P<0.05) in 'Beihua No.1' and 0.73(P<0.05) in 'Sijihua'. The antioxidant activity of both varieties was the strongest at the ML and the second at the EB. This study revealed that the content dynamics of iridoids, phenolic acids, and flavonoids in 'Sijihua' and 'Beihua No.1' cultivated in Shandong province during different developmental stages. The results indicated that the antioxidant activity of L. japonica flowers was significantly correlated with the content of phenolic acids at different deve-lopmental stages, which provided a basis for determining the optimum harvest time of L. japonica flowers.

Common Spontaneous Tumors and Tumor-like Lesions in 70 Pet Rodents and Negative MMTV Detection in Mammary Tumors.

Compared to the number of studies on the neoplasms of laboratory rodents, fewer studies have focused on spontaneous neoplasms in pet rodents. Notably, the mouse mammary tumor virus (MMTV) is associated with mammary tumors in rodents. In this study, 77 tumors and tumor-like lesions of biopsy samples were collected from 70 pet rodents, including hamsters (n = 47), guinea pigs (n = 16), unknown species (n = 4), rats (n = 2), and a gerbil. Fifty tumors were collected from 47 hamsters, in which the most common tumors were mammary tumors (13/50), followed by fibrosarcoma (9/50), mast cell tumors (4/50), and squamous cell carcinoma (4/50). The collected subtypes of mammary tumors in hamsters included tubular carcinoma (n = 5), tubular adenoma (n = 4), carcinoma and malignant myoepithelioma (n = 1), simple tubular carcinoma (n = 1), adenosquamous carcinoma (n = 1), and tubulopapillary adenoma (n = 1). In addition, twenty tumors were collected from guinea pigs, in which the most common tumor was lipoma (6/20), followed by adenocarcinoma of the mammary gland (4/20), trichofolliculoma (2/20), and collagenous hamartomas (2/20). In guinea pigs, the subtypes of mammary gland tumors were tubular carcinoma (n = 2), tubular and solid carcinoma (n = 1), and tubulopapillary carcinoma (n = 1). In 20 cases of mammary tumors, MMTV was not detected, implicating no evidence of MMTV infection in mammary oncogenesis in pet rodents in Taiwan.

CauDR: A causality-inspired domain generalization framework for fundus-based diabetic retinopathy grading.

Diabetic retinopathy (DR) is the most common diabetic complication, which usually leads to retinal damage, vision loss, and even blindness. A computer-aided DR grading system has a significant impact on helping ophthalmologists with rapid screening and diagnosis. Recent advances in fundus photography have precipitated the development of novel retinal imaging cameras and their subsequent implementation in clinical practice. However, most deep learning-based algorithms for DR grading demonstrate limited generalization across domains. This inferior performance stems from variance in imaging protocols and devices inducing domain shifts. We posit that declining model performance between domains arises from learning spurious correlations in the data. Incorporating do-operations from causality analysis into model architectures may mitigate this issue and improve generalizability. Specifically, a novel universal structural causal model (SCM) was proposed to analyze spurious correlations in fundus imaging. Building on this, a causality-inspired diabetic retinopathy grading framework named CauDR was developed to eliminate spurious correlations and achieve more generalizable DR diagnostics. Furthermore, existing datasets were reorganized into 4DR benchmark for DG scenario. Results demonstrate the effectiveness and the state-of-the-art (SOTA) performance of CauDR. Diabetic retinopathy (DR) is the most common diabetic complication, which usually leads to retinal damage, vision loss, and even blindness. A computer-aided DR grading system has a significant impact on helping ophthalmologists with rapid screening and diagnosis. Recent advances in fundus photography have precipitated the development of novel retinal imaging cameras and their subsequent implementation in clinical practice. However, most deep learning-based algorithms for DR grading demonstrate limited generalization across domains. This inferior performance stems from variance in imaging protocols and devices inducing domain shifts. We posit that declining model performance between domains arises from learning spurious correlations in the data. Incorporating do-operations from causality analysis into model architectures may mitigate this issue and improve generalizability. Specifically, a novel universal structural causal model (SCM) was proposed to analyze spurious correlations in fundus imaging. Building on this, a causality-inspired diabetic retinopathy grading framework named CauDR was developed to eliminate spurious correlations and achieve more generalizable DR diagnostics. Furthermore, existing datasets were reorganized into 4DR benchmark for DG scenario. Results demonstrate the effectiveness and the state-of-the-art (SOTA) performance of CauDR.

Effects of cooking with solid fuel on hearing loss in Chinese adults-Based on two cohort studies.

The association between cooking fuel and hearing loss still needs more research to clarify, and two longitudinal cohort studies were explored to find if solid fuel use for cooking affected hearing in Chinese adults. The data from Chinese Health and Retirement Longitudinal Survey (CHARLS) and Chinese Longitudinal Healthy Longevity Survey (CLHLS) were analyzed. Participants (older than 18) without hearing loss at baseline and follow-up visits were included, which were divided into clean fuel and solid fuel groups. Hearing loss rate was from follow-up visits (both in year 2011) until the recent one (year 2018 in CHARLS and 2019 in CLHLS). Cox regressions were applied to examine the associations with adjustment for potential confounders. Fixed-effect meta-analysis was used to pool the results. A total of 9049 participants (average age 8.34 ± 9.12 [mean ± SD] years; 4247 [46.93%] males) were included in CHARLS cohort study and 2265 participants (average age, 78.75 ± 9.23 [mean ± SD] years; 1148 [49.32%] males) in CLHLS cohort study. There were 1518 (16.78%) participants in CHARLS cohort and 451 (19.91%) participants in CLHLS cohort who developed hearing loss. The group of using solid fuel for cooking had a higher risk of hearing loss (CHARLS: HR, 1.16; 95% CI 1.03-1.30; CLHLS: HR, 1.43; 95% CI 1.11-1.84) compared with the one of using clean fuel. Pooled hazard ratio showed the incidence of hearing loss in the solid fuel users was 1.17 (1.03, 1.29) times higher than that of clean fuel users. Hearing loss was associated with solid fuel use and older people were at higher risk. It is advised to replace solid fuel by clean fuel that may promote health equity.

Carbon-nitrogen transmutation in polycyclic arenol skeletons to access N-heteroarenes.

Developing skeletal editing tools is not a trivial task, and realizing the corresponding single-atom transmutation in a ring system without altering the ring size is even more challenging. Here, we introduce a skeletal editing strategy that enables polycyclic arenols, a highly prevalent motif in bioactive molecules, to be readily converted into N-heteroarenes through carbon-nitrogen transmutation. The reaction features selective nitrogen insertion into the C-C bond of the arenol frameworks by azidative dearomatization and aryl migration, followed by ring-opening, and ring-closing (ANRORC) to achieve carbon-to-nitrogen transmutation in the aromatic framework of the arenol. Using widely available arenols as N-heteroarene precursors, this alternative approach allows the streamlined assembly of complex polycyclic heteroaromatics with broad functional group tolerance. Finally, pertinent transformations of the products, including synthesis complex biheteroarene skeletons, were conducted and exhibited significant potential in materials chemistry.

lncRNA SNHG4 inhibits ferroptosis by orchestrating miR-150-5p/c-Myb axis in colorectal cancer.

LncRNAs have shown to regulate ferroptosis in colorectal cancer (CRC), but the mechanism remains largely unknown. This study unveiled the mechanism of SNHG4 underlying ferroptosis in CRC. RNA-seq and RT-PCR assay confirmed SNHG4 was decreased after Erastin treatment in CRC cells. Overexpression of SNHG4 inhibited and silence promoted CRC cells ferroptosis. SNHG4 was positively correlated to c-Myb in CRC tissues and both located in cytoplasm of CRC cells. RIP and RNA pull-down assays verified the interaction between SNHG4 and c-Myb. Silence of c-Myb alleviated the suppressing effect on ferroptosis by SNHG4 in CRC cells. Dual-luciferase reporter assay revealed that SNHG4 sponging miR-150-5p in CRC cells. Overexpression of SNHG4 decreased the miR-150-5p and increased c-Myb expression. c-Myb was a direct target gene of miR-150-5p in CRC cells. Moreover, effect of CDO1 on ferroptosis was regulated transcriptionally by c-Myb, overexpression of c-Myb reduce CDO1 expression and enhance the GPX4 levels. The animal models confirmed that regulatory effect of SNHG4 on miR-150-5p and c-Myb after inducing ferroptosis. We concluded that SNHG4 inhibited Erastin-induce ferroptosis in CRC, this effect is via sponging miR-150-5p to regulate c-Myb expression, and activated CDO1/GPX4 axis. These findings provide insights into the regulatory mechanism of SNHG4 on ferroptosis.

Simultaneous removal of nitrogen, phosphorus, and organic matter from oligotrophic water in a system containing biochar and construction waste iron: Performances and biotic community analysis.

The issue of combined pollution in oligotrophic water has garnered increasing attention in recent years. To enhance the pollutant removal efficiency in oligotrophic water, the system containing Zoogloea sp. FY6 was constructed using polyester fiber wrapped sugarcane biochar and construction waste iron (PWSI), and the denitrification test of simulated water and actual oligotrophic water was carried out for 35 days. The experimental findings from the systems indicated that the removal efficiencies of nitrate (NO3--N), total nitrogen (TN), chemical oxygen demand (COD), and total phosphorus (TP) in simulated water were 88.61%, 85.23%, 94.28%, and 98.90%, respectively. The removal efficiencies of actual oligotrophic water were 83.06%, 81.39%, 81.66%, and 97.82%, respectively. Furthermore, the high-throughput sequencing data demonstrated that strain FY6 was successfully loaded onto the biological carrier. According to functional gene predictions derived from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, the introduction of PWSI enhanced intracellular iron cycling and nitrogen metabolism.

Long-term Efficacy and Safety of High-frequency Spinal Stimulation for Chronic Pain: A Meta-analysis of Randomized Controlled Trial.

OBJECTIVE: The aim of our meta-analysis was to systematically assess the enduring effectiveness and safety of high-frequency spinal stimulation (HF-SCS) in the management of chronic pain. METHODS: We developed a comprehensive literature search strategy to identify clinical trials investigating the efficacy of high-frequency spinal stimulation for chronic pain. The search was conducted in multiple databases, including Web of Science, Cochrane, PubMed, and Embase, covering the period from 2004 to 2023. The inclusion and exclusion criteria established for this study were applied to screen the eligible literature by carefully reviewing abstracts and, when necessary, examining the full text of selected articles. To assess the quality of the included studies, we utilized the risk of bias assessment tool provided by the Cochrane Collaboration.The PRISMA method was followed for the selection of articles, and the quality of the articles was evaluated using the risk assessment table for bias provided by the Cochrane Collaboration.Meta-analysis of the selected studies was performed using Review Manager 5.4 and STATA 16.0. Effect sizes for continuous data were reported as mean differences (MD) or standardized mean differences (SMD), while categorical data were analyzed using relative risks (RR). RESULTS: According to our predefined literature screening criteria, a total of seven English-language randomized controlled trials (RCTs) were included in the meta-analysis. The findings from the meta-analysis demonstrated that high-frequency spinal cord stimulation (HF-SCS) exhibited superior efficacy in the long-term treatment of chronic pain when compared to the control group (RR = 2.44, 95% CI [1.20, 4.96], P = 0.01). Furthermore, HF-SCS demonstrated a statistically significant improvement in the Oswestry Disability Index score (mean difference MD = 3.77, 95% CI [1.17, 6.38], P = 0.005).However, for pain assessment (standardized mean difference SMD = -0.59, 95% CI [-1.28, 0.10], P = 0.09), Patient Global Impression of Improvement (PGI-I) score (MD = 0.11, 95% CI [-0.66, 0.88], P = 0.78 for 6 months; MD = 0.02, 95% CI [-0.42, 0.43], P = 0.97 for 12 months), Clinical Global Impression of Improvement (CGI-I) score (MD = -0.58, 95% CI [-1.62, 0.43], P = 0.27 for 6 months; MD = -0.23, 95% CI [-0.94, 0.48], P = 0.52 for 12 months), and occurrence of adverse effects (odds ratio OR = 0.77, 95% CI [0.23, 2.59], P = 0.67) from a statistical point of view, HF-SCS did not show sufficient effect compared with the control group. Not significant enough to consider it. CONCLUSIONS: The findings from our comprehensive review and meta-analysis, encompassing research from 2004 to 2023, offer encouraging data about the prolonged efficacy and safety of HF-SCS in chronic pain management. Nonetheless, recognizing the constraints of the existing evidence is crucial. Upcoming clinical trials, meticulously planned and stringent, are essential to bolster the current body of evidence and reach more conclusive findings.

A Reconfigurable DNA Framework Nanotube-Assisted Antiangiogenic Therapy.

A major limitation of tumor antiangiogenic therapy is the pronounced off-target effect, which can lead to unavoidable injury in multiple organs. Ensuring sufficient delivery and controlled release of these antiangiogenic agents at tumor sites is crucial for realizing their clinical application. Here, we develop a smart DNA-based nanodrug, termed Endo-rDFN, by precisely assembling the antiangiogenic agent, endostar (Endo), into a reconfigurable DNA framework nanotube (rDFN) that could recognize tumor-overexpressed nucleolin to achieve the targeted delivery and controllable release of Endo. Endo-rDFN can not only effectively enhance the tumor-targeting capability of Endo and maintain its efficient accumulation in tumor tissues but also achieve on-demand release of Endo at tumor sites via the specific DNA aptamer for tumor-overexpressed nucleolin, named AS1411. We also found that Endo-rDFN exhibited significant inhibition of angiogenesis and tumor growth, while also providing effective protection against multiorgan injury (heart, liver, spleen, kidney, lung, etc.) to some extent, without compromising the function of these organs. Our study demonstrates that rDFN represents a promising vector for reducing antiangiogenic therapy-induced multiorgan injury, highlighting its potential for promoting the clinical application of antiangiogenic agents.

Antimicrobial resistance profile in Salmonella enterica serovar Choleraesuis isolates from diseased pigs in Taiwan.

This study investigated antimicrobial resistance in Salmonella enterica serovar Choleraesuis (S. Choleraesuis) isolates from diseased pigs in Taiwan (2015-2020). Among 272 isolates, florfenicol (96.7%), enrofloxacin (96.3%), doxycycline (91.2%), gentamicin (84.6%), and tiamulin (80.5%) exhibited high resistance. 99.3% of the isolates were resistant to at least one antibiotic, and 97.8% of the isolates were multidrug resistant. This study illustrated that S. Choleraesuis isolates exhibited high resistance to antimicrobials currently used in the Taiwanese swine industry.

Poor sleep quality and its associated factors among working adults during COVID-19 pandemic in Malaysia.

Background: In Malaysia, a nationwide movement control order (MCO), implemented to curb the COVID-19 spread, impacted on the lives of the working population which could impair sleep quality. Objective: This study aims to find the sleep quality status and its association with the socioeconomic, employment and lifestyle factors of working adults during the MCO period. Methods: A cross-sectional study was conducted among 500 eligible working adults. Data were collected using a structured questionnaire consisting of the Pittsburg Sleep Quality Index. Results: The proportion of poor sleep quality is found to be 59.4%. Analysis shows that the use of electronic devices before sleep (OR = 2.33, 95% CI = 1.02-5.35, p-value = 0.046), increased amount of workload (OR = 0.45, p-value = 0.005), decreased in amount of workload (OR = 0.48, p-value = 0.003) and distracted while working (OR = 0.57, p-value = 0.014) are the factors significantly associated with and are predictors of poor sleep quality. Conclusion: During crisis, there is a need for public health interventions for the working population to adopt a healthy lifestyle. Employers are recommended to support employees' well-being and to provide a healthy workplace during challenging times. Policy recommendations are also made to implement flexible working arrangements, workload management, workplace mental health support and legal protections on reasonable working hours, rest breaks and time off during crises.