In situ electron generation through Fe/C supported sludge coupled with a counter-diffusion biofilm for electron-deficient wastewater treatment: Binding properties and catalytic competition mechanism of nitrate reductase.

A membrane-aerated biofilm-coupled Fe/C supported sludge system (MABR-Fe/C) was constructed to achieve in situ electron production for NO3--N reduction enhancement in different Fe/C loadings (10 g and 200 g). The anoxic environment formed in the MABR-Fe/C promoted a continual Fe2+release of Fe/C in 120 d operation (average Fe2+concentrations is 1.18 and 2.95 mg/L in MABR-Fe/C10 and MABR-Fe/C200, respectively). Metagenomics results suggested that the electrons generated from ongoing Fe2+ oxidation were transferred via the Quinone pool to EC 1.7.5.1 rather than EC 1.9.6.1 to complete the process of NO3--N reduction to NO2--N in Acidovorax, Ottowia, and Polaromonas. In the absence of organic matter, the NO3--N removal in MABR-Fe/C10 and MABR-Fe/C200 increased by 11.99 and 12.52 mg/L, respectively, compared to that in MABR. In the further NO2--N reduction, even if the minimum binding free energy (MBFE) was low, NO2--N in Acidovorax and Dechloromonas preferentially bind the Gln-residues for dissimilatory nitrate reduction (DNR) in the presence of Fe/C. Increasing Fe/C loading (MABR-Fe/C200) caused the formation of different residue binding sites, further enhancing the already dominant DNR. When DNR in MABR-Fe/C200 intensified, the TN in the effluent increased by 3.75 mg/L although the effluent NO3--N concentration was lower than that in MABR-Fe/C10. This study demonstrated a new MABR-Fe/C system for in situ electron generation to enhance biological nitrogen removal and analyzed the NO3--N reduction pathway and metabolic mechanism, thus providing new ideas for nitrogen removal in electron-deficient wastewater.

Preventive effect of Lactobacillus johnsonii YH1136 against uric acid accumulation and renal damages.

Background: Hyperuricemia (HUA) is a prevalent metabolic disorder whose development is associated with intestinal microbiota. Therefore, probiotics have emerged as a potential and safe approach for lowering uric acid (UA) levels. However, the underlying mechanisms of many effective probiotic strains remain unknown. Methods and results: C57BL/6 mice were randomly divided into two groups: control and model groups. The model group received 12 weeks of potassium oxonate. Through 16s sequencing we found that HUA resulted in a significant decrease in the total diversity of all intestinal segments. When each intestinal segment was analyzed individually, the reduction in diversity was only significant in the cecum and colon sections. RDA analysis showed that lactobacilli in the rat colon exhibited a strong correlation with model group, suggesting that Lactobacillus may play an important role in HUA. Consequently, the preventive effects of Lactobacillus johnsonii YH1136 against HUA were investigated. C57BL/6 mice were randomly divided into three groups: control, model and YH1136 groups. The results showed that administering Lactobacillus johnsonii YH1136 effectively reduced serum UA levels in vivo by inhibiting hepatic xanthine oxidase (XOD) activity and promoting renal ABCG2 transporter expression. Moreover, supplementation with Lactobacillus johnsonii YH1136 significantly ameliorated pathological damage in the kidney and liver, thereby reducing UA accumulation. Conclusion: Hyperuricemia is accompanied by an altered composition of multiple gut bacteria, of which Lactobacillus is a key genus. Lactobacillus johnsonii YH1136 may ameliorate renal involvement in HUA via the gut-kidney axis.

Cobalt single-atom catalyst tailored ceramic membrane for selective removal of emerging organic contaminants.

Water reuse is an effective way to solve the issues of current wastewater increments and water resource scarcity. Ultrafiltration, a promising method for water reuse, has the characteristics of low energy consumption, easy operation, and high adaptability to coupling with other water treatment processes. However, emerging organic contaminants (EOCs) in municipal wastewater cannot be effectively intercepted by ultrafiltration, which poses significant challenges to the effluent quality and sustainability of ultrafiltration process. Here, we develop a cobalt single-atom catalyst-tailored ceramic membrane (Co1-NCNT-CM) in conjunction with an activated peroxymonosulfate (PMS) system, achieving excellent EOCs degradation and anti-fouling performance. An interfacial reaction mechanism effectively mitigates membrane fouling through a repulsive interaction with natural organic matter. The generation of singlet oxygen at the Co-N3-C active sites through a catalytic pathway (PMS→PMS∗→OH∗→O∗→OO∗→1O2) exhibits selective oxidation of phenols and sulfonamides, achieving >90% removal rates. Our findings elucidate a multi-layered functional architecture within the Co1-NCNT-CM/PMS system, responsible for its superior performance in organic decontamination and membrane maintenance during secondary effluent treatment. It highlights the power of integrating Co1-NCNT-CM/PMS systems in advanced wastewater treatment frameworks, specifically for targeted EOCs removal, heralding a new direction for sustainable water management.

An integrated transcriptomics and network pharmacology approach to explore the mechanism of Wang-Bi tablet against SAPHO syndrome.

BACKGROUND: SAPHO syndrome is recognized as a rare entity with damage to skin and bones due to inflammation. Currently, the treatment for SAPHO syndrome is still a challenge in clinical practice. In this study, an integrated transcriptomics and network pharmacology approach was applied to explore the therapeutic effect and mechanism of Wang-Bi tablet (WBT) on SAPHO syndrome. METHODS: The main components of WBT and their targets, as well as the targets of SAPHO syndrome, were collected from databases. Network visualization was performed using Cytoscape software. The GO and KEGG enrichment analysis was executed by David dataset. Then, the molecular mechanism of WBT improving SAPHO syndrome was validated by transcriptomics of peripheral blood neutrophils in SAPHO syndrome. Finally, the above results were validated by molecular docking. RESULTS: The Network Pharmacology results showed there are 152 core targets for WBT treatment on SAPHO syndrome. RNA-seq data showed 442 differentially expressed genes (DEGs) in peripheral blood neutrophils of SAPHO patients. Intriguingly, NIK/NF-kappaB-, MyD88-dependent toll-like receptor-, and MAPK pathway were included in the enrichment results of network pharmacology and RNA-seq. Moreover, we verified that the core components of WBT have good affinity with the core targets of NIK/NF-kappaB-, MyD88-dependent toll-like receptor-, and MAPK pathway by molecular docking. CONCLUSIONS: This study illustrated that the possible mechanisms of WBT against SAPHO syndrome may be related to NIK/NF-kappaB-, MyD88-dependent toll-like receptor-, and MAPK pathway, and further experiments are needed to prove these predictions.

Multiclass classification of motor imagery tasks based on multi-branch convolutional neural network and temporal convolutional network model.

Motor imagery (MI) is a cognitive process wherein an individual mentally rehearses a specific movement without physically executing it. Recently, MI-based brain-computer interface (BCI) has attracted widespread attention. However, accurate decoding of MI and understanding of neural mechanisms still face huge challenges. These seriously hinder the clinical application and development of BCI systems based on MI. Thus, it is very necessary to develop new methods to decode MI tasks. In this work, we propose a multi-branch convolutional neural network (MBCNN) with a temporal convolutional network (TCN), an end-to-end deep learning framework to decode multi-class MI tasks. We first used MBCNN to capture the MI electroencephalography signals information on temporal and spectral domains through different convolutional kernels. Then, we introduce TCN to extract more discriminative features. The within-subject cross-session strategy is used to validate the classification performance on the dataset of BCI Competition IV-2a. The results showed that we achieved 75.08% average accuracy for 4-class MI task classification, outperforming several state-of-the-art approaches. The proposed MBCNN-TCN-Net framework successfully captures discriminative features and decodes MI tasks effectively, improving the performance of MI-BCIs. Our findings could provide significant potential for improving the clinical application and development of MI-based BCI systems.

Replacing traditional pretreatment in one-step UF with natural short-distance riverbank filtration: Continuous contaminants removal and TMP increase relief.

Scientists have been focusing on applying more natural processes instead of industrial chemicals in drinking water treatment to achieve the purpose of carbon emissions reduction. In this study, we shortened the infiltration range of riverbank filtration, a natural water purification process, to form the short-distance riverbank filtration (sRBF) which retained its ability in water quality improvement and barely influenced the groundwater environment, and integrated it with ultrafiltration (UF) to form a one-step sRBF-UF system. This naturalness-artificiality combination could realize stable contaminants removal and trans-membrane pressure (TMP) increase relief for over 30 days without dosing chemicals. Generally, both sRBF and UF played the important role in river water purification, and the interaction between them made the one-step sRBF-UF superior in long-term operation. The sRBF could efficiently remove contaminants (90 % turbidity, 60 % total nitrogen, 30 % ammonia nitrogen, and 25 % total organic carbon) and reduce the membrane fouling potential of river water under its optimum operation conditions, i.e., a hydraulic retention time of 48 h, an operation temperature of 20 °C, and a synergistic filter material of aquifer and riverbank soil. Synergistic adsorption, interception, and microbial biodegradation were proved to be the mechanisms of contaminants and foulants removal for sRBF. The sequential UF also participated in the reduction of impurities and especially played a role in intercepting microbial metabolism products and possibly leaked microorganisms from sRBF, assuring the safety of product water. To date, the one-step sRBF-UF was a new attempt to combine a natural process with an artificial one, and realized a good and stable product quality in long-term operation without doing industrial chemicals, which made it a promised alternative for water purification for cities alongside the river.

Three-compartment membrane electrolyzer combining simultaneous desalination and oxidative degradation in treating nanofiltration concentrate.

The complex organic and inorganic solutes present in nanofiltration's purification by-product (NF concentrate, NFC) pose challenges to the water processing procedure. To address this, a three-compartment membrane electrolyzer was proposed that facilitates electro-driven ion migration for crystallization alongside synchronous anodic oxidation for organic degradation. With a hydraulic retention time (HRT) of 5 min and a current exceeding 50 mA, the system effectively separated over 25 % of inorganic salts and accomplished reclamation through crystallization in the concentration compartment. Simultaneously, it achieved oxidation of pollutants by more than 35 % based on the total nitrogen index and removed upwards of 15 % of organic carbon. Notably, the efficiency of pollutant removal correlated strongly with the intensity of the current. Furthermore, this study uncovered two issues encountered during the electrochemical process: membrane fouling and electrode fouling. During concentration, metal cations readily formed organic pollution by complexing with organic pollutants, while the crystallization of inorganics on the surface of anion exchange membranes emerged as a pivotal factor hindering current enhancement, similar to the formation of deposited salt in a solution. Long HRT can lead to electrode contamination and corrosion which subsequently affect current efficiency. Energy consumption verified the feasibility of the electrolyzer for NFC processing. Based on our findings, a current intensity of 100 mA (equivalent to a density of 8 mA/cm2) was deemed optimal, striking a balance between pollutant removal and various limiting factors associated with each pollutant. Consequently, this innovative advancement in membrane electrolyzers helps in overcoming limitations in synergistic desalination, ion recovery, and organic removal, establishing a fundamental component of the abbreviated flow process for future NFC treatment.

Corrigendum: The prognosis value of CONUT and SIS score for recurrent or metastatic esophageal squamous cell carcinoma patients treated with second-line immunotherapy.

[This corrects the article DOI: 10.3389/fonc.2023.1167625.].

Family aggregation and prevalence of other autoimmune diseases in SAPHO syndrome.

Objective: SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis) syndrome is a heterogeneous disease that clinically manifests as chronic inflammatory osteoarticular and dermatological lesions. Few reports have described familial clustering of SAPHO syndrome cases. This research aimed to illustrate the family aggregation of SAPHO syndrome and investigate the prevalence of autoimmune disorders among SAPHO syndrome patients and first-degree relatives in a large cohort. Methods: We retrospectively reviewed the medical records of 233 SAPHO patients diagnosed at Peking Union Medical College Hospital. Direct phone calls were made to each first-degree relatives. All relatives of the patients who reported SAPHO syndrome were asked for a detailed outpatient evaluation. Results: A total of 233 patients and 1227 first-degree relatives were recruited. Six (2.6 %) patients had positive SAPHO family history, including four mother-daughter pairs and two sister pairs. Twenty-one (9.0 %) patients presented at least one kind of autoimmune disease, including 12 rheumatoid arthritis and 4 ulcerative colitis cases. Fifty-eight (24.9 %) SAPHO syndrome patients had 68 (5.5 %) first-degree relatives with at least one autoimmune disorder. The palmoplantar pustulosis, psoriasis vulgaris, and rheumatoid arthritis prevalence in our subjects were each higher than reference rates. Conclusion: This is the first evaluation of familial aggregation for SAPHO syndrome in a large cohort. SAPHO syndrome has a weak familial aggregation. There is a relatively high prevalence of coexisting autoimmune disease among patients with SAPHO syndrome and their first-degree relatives. These results would prompt physicians to screen SAPHO syndrome patients and their family members for concomitant autoimmune diseases. Keypoints: This study suggesting a potential genetic component in the pathogenesis of SAPHO syndrome. This study is the first to evaluate the family aggregation of SAPHO syndrome in a large cohort.

Overlooked flocs in electrocoagulation-based ultrafiltration systems: A new understanding of the structural interfacial properties.

An integrated ferrate-induced electrocoagulation-ultrafiltration (FECUF) process is proposed to cope with the growing demand for water treatment. Although flocs formed during the electrocoagulation (EC) process are useful for contaminant reduction and mitigation of membrane fouling, few studies have been focused on their structures and properties. Herein, we investigated the formation and structural transformations of flocs and their responses to organic matter, as well as the relationships between their interfacial properties and membrane fouling mitigation. It was found that ferrate contributed to the fast formation of flocs during the ferrate-induced electrocoagulation (FEC) process, which accelerated the FECUF process. Physicochemical analyses indicated that the flocs formed in the FEC process were mainly composed of Fe(III)-(hydr)oxides with abundant hydroxyl groups and poor crystallinity, which allowed complexation with NOM. Therefore, the mobilities of the NOM and the soluble coagulant ions were reduced. The responses of flocs to NOM suggested that the period of 0-20 min resulted in the most efficient NOM removal. In addition, two patterns revealed the relationships between the interfacial properties of the small colloidal particles (SCPs) and the membrane filtration performance: i) the decline in the initial flux was closely related to the composition (gel-type substances or metal-(hydr)oxides) of the SCPs and ii) the steady-state flux was influenced by the energy barrier between the SCPs. However, when the SCPs had the same composition, the interfacial properties influenced both the initial flux and the steady-state flux. This study provides an alternative FECUF process for intensive upgrades of centralized water treatment systems.

Immune checkpoint inhibitors combined with or without radio(chemo)therapy for locally advanced or recurrent/metastatic esophageal squamous cell carcinoma.

OBJECTIVE: This study was designed to investigate the efficacy and prognostic factors for immune checkpoint inhibitors (ICIs) combined with or without radio(chemo)therapy and to evaluate their toxicity in patients with locally advanced or recurrent/metastatic esophageal squamous cell carcinoma (LA/RM ESCC). METHODS: In this study, 198 patients with locally advanced or recurrent/metastatic (LA/RM) ESCC who received ICIs combined with or without radiotherapy/chemotherapy in the Department of Radiotherapy of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. Univariate and multivariate analyses were performed to determine the prognostic factors for overall survival (OS) and progression free survival (PFS). The factors affecting treatment response and the occurrences of treatment-related adverse events (trAEs) were analyzed. RESULTS: The median OS and PFS were 30.4 months (95% confidence interval [CI] 15.1-45.7 months) and 15.3 months (95% CI 12.8-17.8 months), respectively. Univariate and multivariate analysis showed that the number of ICI cycles, the intervention of radiotherapy and dysphagia were independent factors affecting OS (Hazard ratio [HR] = 0.39, 2.043 and 0.365, respectively; P = 0.018, 0.001 and 0.032, respectively). The intervention of radiotherapy was an independent factor for PFS (hazard ratio [HR] = 18.149, P = 0.013). The median OS and PFS for patients who had complete response and partial response (Objective response, ORR) were 50.8 months (95% CI 25.8-75.7 months) and 20.5 months (95% CI 14.1-27.0), respectively, which were significantly higher than those in the non-ORR group (OSnon-ORR:17.5 months, 95% CI 14.0-21.0; χ2 = 13.881, P < 0.001; PFSnon-ORR: 12.1 months, 95% CI 10.1-14.1, χ2 = 10.676, P = 0.001). The intervention of radiotherapy could improve treatment response (χ2 = 47.725, P = 0.000). In entire study population, 83 patients (41.9%) had ≥ grade 2 trAEs. CONCLUSIONS: ICIs combined with radiotherapy/chemotherapy are safe and effective in LA/RM ESCC patients. Intervention of radiotherapy, the number of immunotherapy cycles and occurrence of dysphagia affecting the overall survival of LR/RM ESCC patients. Intervention of radiotherapy was an independent prognosis factor for OS and PFS and associated with better treatment response.

Synergistic effect of potassium ferrate and ferrous iron for improving ultrafiltration performance in algae-laden water treatment.

The application of ultrafiltration (UF) technology in algae-laden water is limited due to the serious membrane fouling caused by algal foulants. Herein, a Ferrate/FeSO4(Fe(VI)/Fe(II)) pretreatment was proposed aiming to improve the performance of UF. The results showed that the synergistic of Fe(VI) and Fe(II) significantly increased the zeta potential of Microcystis aeruginosa, which enhanced the agglomerative tendency of algal foulants, and the particle size of flocs remarkably increased due to the in-situ generated Fe(III). Results from dissolved organic carbon (DOC), UV254, K+, and fluorescent spectra indicated that the introduction of Fe(II) avoided the excessive oxidation of Fe(VI) to algal cells and reduced the production of intracellular organic matter (IOM), while the strong coagulation efficiency of in-situ Fe(III) further enhanced the removal effect of algal organics. Meanwhile, the molecular weight distribution showed that macromolecular organics were decomposed into low molecular matters under Fe(VI) oxidation, while the Fe(VI)/Fe(II) process reduced the formation of small molecular matters compared with single Fe(VI) pretreatment. The algal-source fouling was efficaciously mitigated under the optimal experimental condition, the terminal membrane flux could be increased from 0.16 to 0.62, while reversible and irreversible fouling decreased by 67.1% and 64.1%, respectively. Modeling analysis demonstrated that the Fe(VI)/Fe(II) process altered the fouling mechanism by delaying the formation of cake filtration. Membrane interface characterization further indicated that large size algal flocs form a loose cake layer and reduce the deposition of algal pollutants on the membrane surface. The Extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory confirmed that the hydrophobic adsorption between the algal foulant and the membrane was weakened, thus relieving the membrane fouling. Overall, this strategy can be considered for application in improving the UF performance and mitigating algal-source membrane fouling.

Divergent effects of intensified precipitation on primary production in global drylands.

Amplification of hydrological cycle under warming climate is anticipated to result in intensified precipitation characterized by fewer, more intense events and correspondingly longer dry intervals between events, even without major changes in annual total precipitation. Vegetation gross primary production (GPP) in drylands is highly responsive to intensified precipitation, however, how intensified precipitation influences GPP in global drylands is not well understood. Based on multiple satellite datasets from 2001 to 2020 and in-situ measurements, we investigated the effects of intensified precipitation on global drylands GPP under diverse annual total precipitation along the bioclimate gradient. Dry, normal, and wet years were identified as years with annual precipitation anomalies below, within, and above the range of one standard deviation. Intensified precipitation led to increases or decreases of GPP during dry or normal years, respectively. However, such effects were largely weakened during wet years. The responses of GPP to intensified precipitation were mirrored by soil water availability, as intensified precipitation enhanced root zone soil moisture, and thus vegetation transpiration and precipitation use efficiency during dry years. During wet years, root zone soil moisture showed less response to changed precipitation intensity. Land cover types and soil texture regulated the magnitude of the effects along the bioclimate gradient. Under intensified precipitation, shrubland and grassland distributed in drier region with coarse soil texture showed greater increases of GPP during dry years. As global precipitation will likely further intensify, the impacts of intensified precipitation on dryland carbon uptake capacity will be highly diverse along the bioclimate gradients.

Advances of Artificial Intelligence in Anti-Cancer Drug Design: A Review of the Past Decade.

Anti-cancer drug design has been acknowledged as a complicated, expensive, time-consuming, and challenging task. How to reduce the research costs and speed up the development process of anti-cancer drug designs has become a challenging and urgent question for the pharmaceutical industry. Computer-aided drug design methods have played a major role in the development of cancer treatments for over three decades. Recently, artificial intelligence has emerged as a powerful and promising technology for faster, cheaper, and more effective anti-cancer drug designs. This study is a narrative review that reviews a wide range of applications of artificial intelligence-based methods in anti-cancer drug design. We further clarify the fundamental principles of these methods, along with their advantages and disadvantages. Furthermore, we collate a large number of databases, including the omics database, the epigenomics database, the chemical compound database, and drug databases. Other researchers can consider them and adapt them to their own requirements.

The prognosis value of CONUT and SIS score for recurrent or metastatic esophageal squamous cell carcinoma patients treated with second-line immunotherapy.

Objective: To investigate the predictive value of Controlling Nutritional Status (CONUT) score and systemic inflammation (SIS) score in the prognosis, short-term efficacy, and immune-related side effects of patient with recurrent or metastatic esophageal squamous cell carcinoma (R/M ESCC) receiving immunotherapy as second line therapy combined with or without radiotherapy. Methods: Forty-eight patients with R/M ESCC who received second-line therapy with Camrelizumab were retrospectively studied. They were divided into the high and low score groups according to the CONUT and SIS score. Univariate and multivariate analyses were used to analyze factors that might affect patient prognosis and the effects of different CONUT score and SIS on the short-term efficacy and immune-related toxic and side effects of patients. Results: The 1- and 2-year overall survival (OS) and progression-free survival (PFS) rates were 42.9% and 22.5%, and 29.0% and 5.8%, respectively. The CONUT score ranged from 0 to 6 (3.31 ± 1.43), whereas the SIS score ranged from 0 to 2 (1.19 ± 0.73). Multivariate analysis showed that treatment related toxicity, number of cycles of Camrelizumab used, short-term effect and SIS score were independent prognostic factors for OS (P=0.044, 0.021, 0.021, 0.030, respectively), whereas SIS and CONUT scores were independent prognostic factors for PFS (P=0.005, 0.047, respectively). Patients with low CONUT/SIS score had a low incidence rate of immune-related adverse reactions (X2 = 9.735, 5.693; P=0.002, 0.017) and better short-term efficacy (X2 = 4.427, 7.438; P=0.035, 0.006). Conclusion: R/M ESCC patients with low CONUT/SIS score have better prognosis, higher objective response rate, lower incidence of immune-related toxic and side effects after receiving immunotherapy as second-line therapy. CONUT scores and SIS scores may be reliable prognostic indicators for patient receiving immunotherapy as second-line therapy for R/M ESCC.

Controlling ultrafiltration membrane fouling in surface water treatment via combined pretreatment of O3 and PAC: Mechanism investigation on impacts of technological sequence.

In this research, the effects of combined powdered activated carbon (PAC)-ozone (O3) pretreatment on ultrafiltration (UF) performance were comprehensively examined and compared with the conventional O3-PAC pretreatment. The performance of pretreatments on mitigating membrane fouling caused by Songhua River water (SHR) was evaluated by specific flux, membrane fouling resistance distribution, and membrane fouling index. Moreover, the degradation of natural organic matter in SHR was investigated by UV absorbance at 254 nm (UV254), dissolved organic carbon (DOC), and fluorescent organic matter. Results showed that the 100PAC-5O3 process was the most effective in improving the specific flux, with 82.89 % and 58.17 % reductions in the reversible fouling resistance and irreversible fouling resistance respectively. Additionally, the irreversible membrane fouling index was reduced by 20 % relative to 5O3-100PAC. The PAC-O3 process also exhibited superior performance in the degradation of UV254, DOC, three fluorescent components, and three micropollutants in the SHR system compared to O3-PAC pretreatment. The O3 stage played a major role in mitigating membrane fouling, while PAC pretreatment enhanced the oxidation in the subsequent O3 stage during the PAC-O3 process. Furthermore, the Extended Derjaguin-Landau-Verwey-Overbeek theory and pore blocking-cake layer filtration model fitting analysis were employed to explain the mechanisms of membrane fouling mitigation and fouling patterns transformation. It was found that PAC-O3 significantly increased the repulsive interactions between the foulants and the membrane, which restrained the formation of the cake layer filtration stage. Overall, this study evidenced the potential of PAC-O3 pretreatment in surface water treatment applications, providing new insights into the mechanism of controlling membrane fouling and improving the permeate quality.

Brønsted acid-promoted ring-opening and annulation of thioamides and 2H-azirines to synthesize 2,4,5-trisubstituted thiazoles.

In this study, a metal-free synthesis of 2,4,5-trisubstituted thiazoles using 2H-azirines and thioamides is disclosed. Under the catalysis of HClO4, the protocol was realized through a novel chemical bond breaking of 2H-azirine, which is usually achieved using a metal catalyst. It provides an efficient and green route for the synthesis of substituted thiazoles with a broad substrate scope. Preliminary mechanistic studies show that such a reaction may involve a ring-opening reaction, annulation, and a hydrogen atom rearrangement process.

Overview of distinct 5-methylcytosine profiles of messenger RNA in normal and knock-down NSUN2 colorectal cancer cells.

Background: Colorectal cancer (CRC) is a harmful cancer with high morbidity and poor prognosis. There is growing evidence that RNA methylation is closely related to the occurrence of cancer and its malignant biological behavior. N6-methyladenosine (m6A) methylation is the most common RNA modification in eukaryotes, and its multiple regulatory mechanisms in CRC have been elucidated from multiple perspectives. At the same time, the role of 5-methylcytosine (m5C), another important and widely distributed methylation modification, in CRC is far from being elucidated. Methods: In this study, we used RNA immunoprecipitation sequencing combined with bioinformatics methods to identify the m5C peaks on messenger RNA (mRNA) in HCT15 cells and sh-NSUN2 HCT15 cells, understand which transcripts are modified by m5C, and characterize the distribution of m5C modifications. In addition, we performed further bioinformatics analysis of the detected data to initially clarify the potential function of these m5C-modified transcripts. Results: We found significant differences in the distribution of m5C between HCT15 cells and sh-NSUN2 HCT15 cells, suggesting that m5C is likely to play a key role in the occurrence and development of CRC. Furthermore, Gene Ontology (GO) enrichment analysis showed that genes altered by m5C were mainly enriched in phylogeny, synaptic membrane, and transcription factor binding. The Kyoto Encyclopedia of Genes and Genomes (KEGG)pathway analysis showed that the genes altered by m5C are enriched in ECM receptor interaction pathway, the circadian pathway, and the cAMP signaling pathway. Conclusion: Here, our study preliminarily revealed the different distribution patterns of m5C between HCT15 cell and sh-NSUN2 HCT15 cell. Our results open a new window to understand the role of m5C RNA methylation of mRNA in the development of CRC.

Evaluation of neoadjuvant immunotherapy and traditional neoadjuvant therapy for resectable esophageal cancer: a systematic review and single-arm and network meta-analysis.

Objective: This systematic review and meta-analysis aimed to investigate the role of neoadjuvant immunochemotherapy with or without radiotherapy [NIC(R)T] compared to traditional neoadjuvant therapies, without immunotherapy [NC(R)T]. Summary background data: NCRT followed by surgical resection is recommended for patients with early-stage esophageal cancer. However, it is uncertain whether adding immunotherapy to preoperative neoadjuvant therapy would improve patient outcomes when radical surgery is performed following neoadjuvant therapy. Methods: We searched PubMed, Web of Science, Embase, and Cochrane Central databases, as well as international conference abstracts. Outcomes included R0, pathological complete response (pCR), major pathological response (mPR), overall survival (OS) and disease-free survival (DFS) rates. Results: We included data from 5,034 patients from 86 studies published between 2019 and 2022. We found no significant differences between NICRT and NCRT in pCR or mPR rates. Both were better than NICT, with NCT showing the lowest response rate. Neoadjuvant immunotherapy has a significant advantage over traditional neoadjuvant therapy in terms of 1-year OS and DFS, with NICT having better outcomes than any of the other three treatments. There were no significant differences among the four neoadjuvant treatments in terms of R0 rates. Conclusions: Among the four neoadjuvant treatment modalities, NICRT and NCRT had the highest pCR and mPR rates. There were no significant differences in the R0 rates among the four treatments. Adding immunotherapy to neoadjuvant therapy improved 1-year OS and DFS, with NICT having the highest rates compared to the other three modalities. Systematic Review Registration: https://inplasy.com/inplasy-2022-12-0060/, identifier INPLASY2022120060.