Three-dimensional N-doped carbon nanosheets loaded with heterostructured Ni/Ni3ZnC0.7 nanoparticles for selective and efficient CO2 reduction.

Electrocatalytic CO2 reduction (CO2RR) has emerged as a promising approach for converting CO2 into valuable chemicals and fuels to achieve a sustainable carbon cycle. However, the development of efficient electrocatalysts with high current densities and superior product selectivity remains a significant challenge. In this study, we present the synthesis of a porous nitrogen-doped carbon nanosheet loaded with heterostructured Ni/Ni3ZnC0.7 nanoparticles through a facile hydrothermal-calcination method (Ni/Ni3ZnC0.7-NC). Remarkably, the Ni/Ni3ZnC0.7-NC catalyst exhibits outstanding performance towards CO2RR in an H-cell, demonstrating a high CO faradaic efficiency of 92.47% and a current density (jCO) of 15.77 mA cm-2 at 0.87 V vs. RHE. To further explore its potential industrial applications, we constructed a flow cell and a rechargeable Zn-CO2 flow cell utilizing the Ni/Ni3ZnC0.7-NC catalyst as the cathode. Impressively, not only does the Ni/Ni3ZnC0.7-NC catalyst achieve an industrial high current density of 254 mA cm-2 at a voltage of -1.19 V vs. RHE in the flow cell, but it also exhibits a maximum power density of 4.2 mW cm-2 at 22 mA cm-2 in the Zn-CO2 flow cell, while maintaining excellent rechargeability. Density functional theory (DFT) calculations indicate that Ni/Ni3ZnC0.7-NC possesses more spontaneous reaction pathways for CO2 reduction to CO, owing to its heterogeneous structure in contrast to Ni3ZnC0.7-NC and Ni-NC. Consequently, Ni/Ni3ZnC0.7-NC demonstrates accelerated CO2RR reaction kinetics, resulting in improved catalytic activity and selectivity for CO2RR.

Cinnamaldehyde: an effective component of Cinnamomum cassia inhibiting Helicobacter pylori.

ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum cassia Presl (Cinnamomum cassia) is a common traditional Chinese medicine, which can promote the secretion and digestion of gastric juice, improve the function of gastrointestinal tract. Cinnamaldehyde (CA) is a synthetic food flavoring in the Chinese Pharmacopoeia. AIM OF THE STUDY: This study aimed to search for the active ingredient (CA) of inhibiting H. pylori from Cinnamomum cassia, and elucidate mechanism of action, so as to provide the experimental basis for the treatment of H. pylori infection with Cinnamomum cassia. MATERIALS AND METHODS: It's in vitro and in vivo pharmacological properties were evaluated based on minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and an acute gastric inflammation model in mice infected with H. pylori. Drug safety was evaluated using the CCK8 method and high-dose administration in mice. The advantageous characteristics of CA in inhibiting H. pylori were confirmed using acidic conditions and in combination with the antibiotics. The mechanism underlying the action of CA on H. pylori was explored using scanning electron microscopy (SEM), adhesion experiments, biofilm inhibition tests, ATP and ROS release experiments, and drug affinity responsive target stability (DARTS) screening of target proteins. The protein function and target genes were verified by molecular docking and Real-Time quantitative reverse transcription PCR (qRT-PCR). RESULTS: The results demonstrated that CA was found to be the main active ingredient against H. pylori in Cinnamomum cassia in-vitro tests, with a MIC of 8-16 µg/mL. Moreover, CA effectively inhibited both sensitive and resistant H. pylori strains. The dual therapy of PPI + CA exhibited remarkable in vivo efficacy in the acute gastritis mouse model, superior to the standard triple therapy. DARTS, molecular docking, and qRT-PCR results suggested that the target sites of action were closely associated with GyrA, GyrB, AtpA, and TopA, which made DNA replication and transcription impossible, then leading to inhibition of bacterial adhesion and colonization, suppression of biofilm formation, and inhibition ATP and enhancing ROS. CONCLUSIONS: This study demonstrated the suitability of CA as a promising lead drug against H. pylori, The main mechanisms can target GyrA ect, leading to reduce ATP and produce ROS, which induces the apoptosis of bacterial.

Contemporary strategies and approaches for characterizing composition and enhancing biofilm penetration targeting bacterial extracellular polymeric substances.

Extracellular polymeric substances (EPS) constitutes crucial elements within bacterial biofilms, facilitating accelerated antimicrobial resistance and conferring defense against the host's immune cells. Developing precise and effective antibiofilm approaches and strategies, tailored to the specific characteristics of EPS composition, can offer valuable insights for the creation of novel antimicrobial drugs. This, in turn, holds the potential to mitigate the alarming issue of bacterial drug resistance. Current analysis of EPS compositions relies heavily on colorimetric approaches with a significant bias, which is likely due to the selection of a standard compound and the cross-interference of various EPS compounds. Considering the pivotal role of EPS in biofilm functionality, it is imperative for EPS research to delve deeper into the analysis of intricate compositions, moving beyond the current focus on polymeric materials. This necessitates a shift from heavy reliance on colorimetric analytic methods to more comprehensive and nuanced analytical approaches. In this study, we have provided a comprehensive summary of existing analytical methods utilized in the characterization of EPS compositions. Additionally, novel strategies aimed at targeting EPS to enhance biofilm penetration were explored, with a specific focus on highlighting the limitations associated with colorimetric methods. Furthermore, we have outlined the challenges faced in identifying additional components of EPS and propose a prospective research plan to address these challenges. This review has the potential to guide future researchers in the search for novel compounds capable of suppressing EPS, thereby inhibiting biofilm formation. This insight opens up a new avenue for exploration within this research domain.

Functional diversity of apoptotic vesicle subpopulations from bone marrow mesenchymal stem cells in tissue regeneration.

Apoptosis releases numerous apoptotic vesicles that regulate processes such as cell proliferation, immunity, and tissue regeneration and repair. Now, it has also emerged as an attractive candidate for biotherapeutics. However, apoptotic vesicles encompass a diverse range of subtypes, and it remains unclear which specific subtypes play a pivotal role. In this study, we successfully isolated different apoptotic vesicle subtypes based on their sizes and characterized them using NTA and TEM techniques, respectively. We compared the functional variances among the distinct subtypes of apoptotic vesicles in terms of stem cell proliferation, migration, and differentiation, as well as for endothelial cell and macrophage function, effectively identifying subtypes that exhibit discernible functional differences. ApoSEV (with diameter <1000 nm) promoted stem cell proliferation, migration, and multi-potent differentiation, and accelerated skin wound healing of diabetes mouse model, while apoBD (with diameter >1000 nm) played the opposite effect on cell function and tissue regeneration. Lastly, employing protein analysis and gene sequencing techniques, we elucidated the intrinsic mechanisms underlying these differences between different subtypes of apoEVs. Collectively, this study identified that apoptotic vesicle subtypes possessed distinct bio-functions in regulating stem cell function and behaviour and modulating tissue regeneration, which primarily attribute to the distinct profiling of protein and mRNA in different subtypes. This comprehensive analysis of specific subtypes of apoEVs would provide novel insights for potential therapeutic applications in cell biology and tissue regeneration.

Pre-operative enhanced magnetic resonance imaging combined with clinical features predict early recurrence of hepatocellular carcinoma after radical resection.

BACKGROUND: Indentifying predictive factors for postoperative recurrence of hepatocellular carcinoma (HCC) has great significance for patient prognosis. AIM: To explore the value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) combined with clinical features in predicting early recurrence of HCC after resection. METHODS: A total of 161 patients with pathologically confirmed HCC were enrolled. The patients were divided into early recurrence and non-early recurrence group based on the follow-up results. The clinical, laboratory, pathological results and Gd-EOB-DTPA enhanced MRI imaging features were analyzed. RESULTS: Of 161 patients, 73 had early recurrence and 88 were had non-early recurrence. Univariate analysis showed that patient age, gender, serum alpha-fetoprotein level, the Barcelona Clinic Liver Cancer stage, China liver cancer (CNLC) stage, microvascular invasion (MVI), pathological satellite focus, tumor size, tumor number, tumor boundary, tumor capsule, intratumoral necrosis, portal vein tumor thrombus, large vessel invasion, nonperipheral washout, peritumoral enhancement, hepatobiliary phase (HBP)/tumor signal intensity (SI)/peritumoral SI, HBP peritumoral low signal and peritumoral delay enhancement were significantly associated with early recurrence of HCC after operation. Multivariate logistic regression analysis showed that patient age, MVI, CNLC stage, tumor boundary and large vessel invasion were independent predictive factors. External data validation indicated that the area under the curve of the combined predictors was 0.861, suggesting that multivariate logistic regression was a reasonable predictive model for early recurrence of HCC. CONCLUSION: Gd-EOB-DTPA enhanced MRI combined with clinical features would help predicting the early recurrence of HCC after operation.

Risk factors of central catheter bloodstream infections in intensive care units: A systematic review and meta-analysis.

BACKGROUND: Central catheter bloodstream infections (CRBSI) is a major cause of healthcare-associated infections. However, few factors are generally accepted and some studies have conflicting finding about some factors, possibly caused by limitation associated with an individual study. This study was to identify risk factors for CRBSI in intensive care units. METHODS: We searched the PubMed, Cochrane Library, Web of science and EMBASE databases and the 4 top Chinese-language databases, including WanFang data, China National Knowledge Infrastructure (CNKI), and Chinese Science and Technology Journal Database (VIP), China Biology Medicine disc (CBM) as of July 2023. Case control and cohort studies were included. Two authors independently screened the literature and evaluated the quality of the studies using the Newcastle-Ottawa scale (NOS). The pooled effect size was estimated using the odds ratio (OR), and the corresponding 95% confidence interval (CI) was calculated. The Cochrane Q (χ2) and I2 tests were used to assess heterogeneity among studies, and each risk factor was tested for its robustness using fixed- or random-effects models. FINDINGS: A total of 32 studies enrolled, among which eleven factors were identified, they were divided into two categories: modifiable and unmodifiable factors. Modifiable factors: duration of catheterization (≥ 5d) (OR: 2.07, 95%CI: 1.41-3.03), duration of catheterization (≥ 7d) (OR: 3.62, 95%CI: 2.65-4.97), duration of catheterization (≥ 14d)(OR: 4.85, 95%CI: 3.35-7.01), total parenteral nutrition (OR: 2.27,95%CI: 1.56-3.29), use of multiple-lumen catheters(OR: 3.41, 95%CI: 2.27-5.11), times of tube indwelling (OR: 3.50, 95%CI: 2.93-4.17), length of ICU stay (OR: 4.05, 95%CI: 2.41-6.80), the position of indwelling(OR: 2.41, 95%CI: 2.03-2.85); Unmodifiable factors: APACHEII scores (OR: 1.84, 95%CI: 1.54-2.20), Age≥ 60 years old (OR: 2.19, 95%CI: 1.76-2.73), the extensive use of antibiotic (OR: 3.54, 95%CI: 1.65-7.61), Diabetes mellitus (OR: 3.06, 95%CI: 2.56-3.66), Immunosuppression (OR: 2.87, 95%CI: 2.08-3.95). CONCLUSIONS: Effective interventions targeting the above modifiable factors may reduce the risk of developing CRBSI in ICU and improve the clinical outcome of patients. Further prospective studies are needed to confirm these findings.

SF3A2 promotes progression and cisplatin resistance in triple-negative breast cancer via alternative splicing of MKRN1.

Triple-negative breast cancer (TNBC) is the deadliest subtype of breast cancer owing to the lack of effective therapeutic targets. Splicing factor 3a subunit 2 (SF3A2), a poorly defined splicing factor, was notably elevated in TNBC tissues and promoted TNBC progression, as confirmed by cell proliferation, colony formation, transwell migration, and invasion assays. Mechanistic investigations revealed that E3 ubiquitin-protein ligase UBR5 promoted the ubiquitination-dependent degradation of SF3A2, which in turn regulated UBR5, thus forming a feedback loop to balance these two oncoproteins. Moreover, SF3A2 accelerated TNBC progression by, at least in part, specifically regulating the alternative splicing of makorin ring finger protein 1 (MKRN1) and promoting the expression of the dominant and oncogenic isoform, MKRN1-T1. Furthermore, SF3A2 participated in the regulation of both extrinsic and intrinsic apoptosis, leading to cisplatin resistance in TNBC cells. Collectively, these findings reveal a previously unknown role of SF3A2 in TNBC progression and cisplatin resistance, highlighting SF3A2 as a potential therapeutic target for patients with TNBC.

Pedigree Analysis of Nonclassical Cholesteryl Ester Storage Disease with Dominant Inheritance in a LIPA I378T Heterozygous Carrier.

BACKGROUND: Cholesterol ester storage disorder (CESD; OMIM: 278,000) was formerly assumed to be an autosomal recessive allelic genetic condition connected to diminished lysosomal acid lipase (LAL) activity due to LIPA gene abnormalities. CESD is characterized by abnormal liver function and lipid metabolism, and in severe cases, liver failure can occur leading to death. In this study, one Chinese nonclassical CESD pedigree with dominant inheritance was phenotyped and analyzed for the corresponding gene alterations. METHODS: Seven males and eight females from nonclassical CESD pedigree were recruited. Clinical features and LAL activities were documented. Whole genome Next-generation sequencing (NGS) was used to screen candidate genes and mutations, Sanger sequencing confirmed predicted mutations, and qPCR detected LIPA mRNA expression. RESULTS: Eight individuals of the pedigree were speculatively thought to have CESD. LAL activity was discovered to be lowered in four living members of the pedigree, but undetectable in the other four deceased members who died of probable hepatic failure. Three of the four living relatives had abnormal lipid metabolism and all four had liver dysfunctions. By liver biopsy, the proband exhibited diffuse vesicular fatty changes in noticeably enlarged hepatocytes and Kupffer cell hyperplasia. Surprisingly, only a newly discovered heterozygous mutation, c.1133T>C (p. Ile378Thr) on LIPA, was found by gene sequencing in the proband. All living family members who carried the p.I378T variant displayed reduced LAL activity. CONCLUSIONS: Phenotypic analyses indicate that this may be an autosomal dominant nonclassical CESD pedigree with a LIPA gene mutation.

Effects of surface nanomorphology on the senescence of periodontal ligament stem cells.

OBJECTIVES: The effect of TiO2 nanotube morphology on the differentiation potency of senescent periodontal ligament stem cells was investigated. METHODS: Two types of titanium sheets with TiO2 nanotube morphology (20V-NT and 70V-NT) were prepared via anodic oxidation at 20 and 70 V separately, and their surface morphology was observed. Young periodontal ligament stem cells were cultivated in an osteogenic induction medium, and the most effective surface morphology in promoting osteogenic differentiation was selected. RO3306 and Nutlin-3a were used to induce the aging of young periodontal ligament stem cells, and senescent periodontal ligament stem cells were obtained. The osteogenic differentiation of senescent periodontal ligament stem cells was induced, and the effect of surface morphology on osteogenic differentiation was observed. RESULTS: Nanotube morphology was achieved on the surfaces of titanium sheets through anodic oxidation, and the diameters of the nanotubes increased with voltage. A significant difference in the effect of nanotube morphology was found among nanotubes with different diameters in the young periodontal ligament stem cells. The surface nanotube morphology of 20V-NT had a more significant effect that promoted osteogenic differentiation. Compared with a smooth titanium sheet, the surface nanotube morphology of 20V-NT increased the number of alkaline phosphatase-positive senescent periodontal ligament stem cells and promoted calcium deposition and the expression of osteogenic marker genes Runt-related transcription factor 2, osteopontin, and osteocalcin. CONCLUSIONS: A special nanotube morphology enhances the differentiation ability of senescent periodontal ligament stem cells, provides an effective method for periodontal regeneration, and further improves the performance of implants.

The effect of refined psychological pain nursing combined with IMB nursing on the pain, sleep and quality of life of patients after cervical cancer surgery.

To explore the effect of refined psychological pain nursing combined with information-motivation-behavioral (IMB) care model on the pain, sleep and quality of life of patients after cervical cancer surgery, so as to provide reference and basis for the nursing of patients after cervical cancer surgery. The clinical data of 798 postoperative cervical cancer patients who were nursing in our hospital from January 2018 to December 2022 were included in this retrospective study and divided into the control group (n = 382) and observation group (n = 416) according to the different care methods. The control group used refined psychological pain nursing, and on this basis, the observation group used IMB nursing to observe and compare the differences in pain, sleep and quality of life between the 2 groups. There was no significant difference in pain between the 2 groups before nursing (P > .05). After nursing, the pain of both groups was significantly improved. The scores of NRS, VAS, and PSEQ of the observation group were significantly better than those of the control group (P < .001). After nursing, the quality of life scores such as emotion, cognition, society, and overall health were significantly higher in the observation group than those of the control group, while physical, fatigue, nausea, vomiting, and pain were significantly lower than those of the control group (P < .05). The negative emotion score of the observation group was significantly lower than that of the control group (P < .001). The residual urine volume and urinary tract infection rate of the observation group were significantly lower than those of the control group (P < .05). The bladder function was significantly better than that of the control group (P < .05). The analgesic effect of refined psychological pain nursing combined with IMB nursing on patients after cervical cancer surgery is better than that of refined psychological pain nursing alone, which can promote pain recovery and further improve the quality of life and sleep quality of patients.

Partially knocking out NtPDK1a/1b/1c/1d simultaneously in Nicotiana tabacum using CRISPR/CAS9 technology results in auxin-related developmental defects.

The eukaryotic AGC protein kinase subfamily (protein kinase A/ protein kinase G/ protein kinase C-family) is involved in regulating numerous biological processes across kingdoms, including growth and development, and apoptosis. PDK1(3-phosphoinositide-dependent protein kinase 1) is a conserved serine/threonine kinase in eukaryotes, which is both a member of AGC kinase and a major regulator of many other downstream AGC protein kinase family members. Although extensively investigated in model plant Arabidopsis, detailed reports for tobacco PDK1s have been limited. To better understand the functions of PDK1s in tobacco, CRISPR/CAS9 transgenic lines were generated in tetraploid N. tabacum, cv. Samsun (NN) with 5-7 of the 8 copies of 4 homologous PDK1 genes in tobacco genome (NtPDK1a/1b/1c/1d homologs) simultaneously knocked out. Numerous developmental defects were observed in these NtPDK1a/1b/1c/1d CRISPR/CAS9 lines, including cotyledon fusion leaf shrinkage, uneven distribution of leaf veins, convex veins, root growth retardation, and reduced fertility, all of which reminiscence of impaired polar auxin transport. The severity of these defects was correlated with the number of knocked out alleles of NtPDK1a/1b/1c/1d. Consistent with the observation in Arabidopsis, it was found that the polar auxin transport, and not auxin biosynthesis, was significantly compromised in these knockout lines compared with the wild type tobacco plants. The fact that no homozygous plant with all 8 NtPDK1a/1b/1c/1d alleles being knocked out suggested that knocking out 8 alleles of NtPDK1a/1b/1c/1d could be lethal. In conclusion, our results indicated that NtPDK1s are versatile AGC kinases that participate in regulation of tobacco growth and development via modulating polar auxin transport. Our results also indicated that CRISPR/CAS9 technology is a powerful tool in resolving gene redundancy in polyploidy plants.

Adult type I Gaucher disease with splenectomy caused by a compound heterozygous GBA1 mutation in a Chinese patient: a case report.

Gaucher disease (GD) is an autosomal recessive ailment resulting from glucocerebrosidase deficiency caused by a mutation in the GBA1 gene, leading to multi-organ problems in the liver, spleen, and bone marrow. In China, GD is extremely uncommon and has a lower incidence rate than worldwide. In this study, we report the case of an adult male with an enlarged spleen for 13 years who presented with abdominal distension, severe loss of appetite and weight, reduction of the three-line due to hypersplenism, frequent nosebleeds, and bloody stools. Regrettably, the unexpected discovery of splenic pathology suggestive of splenic Gaucher disease was only made after a splenectomy due to a lack of knowledge about rare disorders. Our patient's delayed diagnosis may have been due to the department where he was originally treated, but it highlights the need for multidisciplinary consultation in splenomegaly of unknown etiology. We then investigated the patient's clinical phenotypes and gene mutation features using genetically phenotypical analysis. The analysis of the GBA1 gene sequence indicated that the patient carried a compound heterozygous mutation consisting of two potentially disease-causing mutations: c.907C > A (p. Leu303Ile) and c.1448 T > C (p. Leu483Pro). While previous research has linked the p. Leu483Pro mutation site to neurologic GD phenotypes (GD2 and GD3), the patients in this investigation were identified as having non-neuronopathic GD1. The other mutation, p. Leu303Ile, is a new GD-related mutation not indexed in PubMed that enriches the GBA1 gene mutation spectrum. Biosignature analysis has shown that both mutations alter the protein's three-dimensional structure, which may be a pathogenic mechanism for GD1 in this patient.

DNA Damage-Induced Apoptosis Suppressor Triggers Progression and Stemness of Glioma by Enhancing Lymphoid Enhancer-Binding Factor 1 Expression.

Background: DNA damage-induced apoptosis suppressor (DDIAS) has recently been discovered to induce cancer progression, but its functions and mechanisms in glioma have not been well studied. Methods: DDIAS expression in glioma tissues was analyzed by the Gene Expression Profiling Interactive Analysis server (GEPIA) and the Gene Expression database of Normal and Tumor tissue 2 (GENT2) databases. The role of DDIAS in glioma progression was studied by short hairpin RNA (shRNA) targeting DDIAS. The effects of DDIAS on glioma cell viability, cell proliferation, invasion, migration, and tumor sphere formation were determined by cell counting kit-8 (CCK-8), EdU, Transwell, tumor spheroid formation, extreme limiting dilution analysis assays in vitro and xenograft model construction in vivo. In addition, RNA sequencing and further functional experiments were used to analyze the DDIAS regulatory mechanism in glioma. Results: We found that DDIAS was highly expressed in glioma and that upregulated DDIAS indicated poor prognosis. Functionally, DDIAS knockdown inhibited glioma cell viability, cell proliferation, invasion and migration in vitro and tumor growth in vivo. In addition, lymphoid enhancer-binding factor 1 (LEF1) was identified as the downstream effector of DDIAS by RNA sequencing. DDIAS downregulation inhibited LEF1 mRNA and protein expression. The expression of DDIAS and LEF1 was positively correlated, and LEF1 overexpression rescued the inhibitory phenotype induced by DDIAS downregulation. We further showed that DDIAS downregulation inhibited cyclin A1, vimentin and the stemness-related factor CD133 and decreased the sphere formation capability, but these features were rescued by upregulation of LEF1. Conclusion: Taken together, these findings suggest that DDIAS promotes glioma progression and stemness by inducing LEF1 expression, proving that DDIAS may be a potential target for the treatment of glioma.

Size-selective sampler combined with an immunochromatographic assay for the rapid detection of airborne Legionella pneumophila.

Airborne biological aerosols (also called bioaerosols) are found in various environmental and occupational settings. Among these, pathogenic bioaerosols can cause diseases such as legionellosis, influenza, measles, and tuberculosis. To prevent or minimize people's exposure to these pathogenic bioaerosols in the field, a rapid detection method is required. In this study, a size-selective bioaerosol (SSB) sampler was combined with the immunochromatographic assay (ICA). The SSB sampler can collect bioaerosols on the sampling swab and the lateral flow test kit used in ICA can rapidly detect the pathogens in bioaerosols collected on the swab. Before testing the combined method, the lower limit of detection (LOD) of the lateral flow test kit was determined. Legionella pneumophila (L. pneumophila) was used as a target pathogen. The results show that at least 1.3 × 103L. pneumophila cells are required to be detected by the lateral flow test kit. To test the developed method, L. pneumophila suspension was aerosolized in the sampling chamber and collected using two SSB samplers with different sampling times (10 and 20 min). The developed method could detect aerosolized L. pneumophila and also estimate the concentrations from the lower LOD, sampling time, and formation of a positive line on a test strip. When positive results were obtained from sampling for 10 min and 20 min, concentrations of respirable L. pneumophila were estimated ≥5.2 × 104 CFUresp/m3 and ≥2.6 × 104 CFUresp/m3, respectively. The conventional sampler Andersen impactor with colony counting was also used for comparison. In all cases, the estimated concentrations obtained by the developed method were higher than those obtained by the conventional method. These findings confirm that the developed method can overcome the limitations of conventional methods and eventually benefit environmental and occupational health by providing a better method for risk assessment.

Atropisomeric Carboxylic Acids Synthesis via Nickel-Catalyzed Enantioconvergent Carboxylation of Aza-Biaryl Triflates with CO2.

Upgrading CO2 to value-added chiral molecules via catalytic asymmetric C-C bond formation is a highly important yet challenging task. Although great progress on the formation of centrally chiral carboxylic acids has been achieved, catalytic construction of axially chiral carboxylic acids with CO2 has never been reported to date. Herein, we report the first catalytic asymmetric synthesis of axially chiral carboxylic acids with CO2, which is enabled by nickel-catalyzed dynamic kinetic asymmetric reductive carboxylation of racemic aza-biaryl triflates. A variety of important axially chiral carboxylic acids, which are valuable but difficult to obtain via catalysis, are generated in an enantioconvergent version. This new methodology features good functional group tolerance, easy to scale-up, facile transformation and avoids cumbersome steps, handling organometallic reagents and using stoichiometric chiral materials. Mechanistic investigations indicate a dynamic kinetic asymmetric transformation process induced by chiral nickel catalysis.

MicroRNA-126 (MiR-126): key roles in related diseases.

In eukaryotes such as humans, some non-coding single-stranded RNAs (ncRNAs) help to regulate the pre- and post-transcriptional expression of certain genes, which in turn control many important physiological processes, such as cell proliferation, distinctions, invasion, angiogenesis, and embryonic development. microRNA-126 is an important member of these miRNAs that can be directly or indirectly involved in the control of angiogenesis. Recently, numerous studies have expounded that microRNA-126 can inhibit or promote angiogenesis as well as attenuate inflammatory responses through complex molecular mechanisms. As such, it serves as a biomarker or potential therapeutic target for the prediction, diagnosis, and treatment of relevant diseases. In this review, we present the advancements in research regarding microRNA-126's role in the diagnosis and treatment of related diseases, aiming to provide innovative therapeutic options for the diagnosis and treatment of clinically relevant diseases.

Identification of macrophage-related molecular subgroups and risk signature in colorectal cancer based on a bioinformatics analysis.

Macrophages play a crucial role in tumor initiation and progression, while macrophage-associated gene signature in colorectal cancer (CRC) patients has not been investigated. Our study aimed to identify macrophage-related molecular subgroups and develop a macrophage-related risk model to predict CRC prognosis. The mRNA expression profile and clinical information of CRC patients were obtained from TCGA and GEO databases. CRC patients from TCGA were divided into high and low macrophage subgroups based on the median macrophage score. The ESTIMATE and CIBERSORT algorithms were used to assess immune cell infiltration between subgroups. GSVA and GSEA analyses were performed to investigate differences in enriched pathways between subgroups. Univariate and LASSO Cox regression were used to build a prognostic risk model, which was further validated in the GSE39582 dataset. A high macrophage score subgroup was associated with poor prognosis, highly activated immune-related pathways and an immune-active microenvironment. A total of 547 differentially expressed macrophage-related genes (DEMRGs) were identified, among which seven genes (including RIMKLB, UST, PCOLCE2, ZNF829, TMEM59L, CILP2, DTNA) were identified by COX regression analyses and used to build a risk score model. The risk model shows good predictive and diagnostic values for CRC patients in both TCGA and GSE39852 datasets. Furthermore, multivariate Cox regression analysis showed that the risk score was an independent risk factor for overall survival in CRC patients. Our findings provided a novel insight into macrophage heterogeneity and its immunological role in CRC. This risk score model may serve as an effective prognostic tool and contribute to personalised clinical management of CRC patients.

Total Synthesis and Antibacterial Evaluation of Lupinifolin and Its Natural Analogues.

In this study, lupinifolin (1) and its natural analogues, mundulin (2), minimiorin (3), khonklonginol H (4), flemichin D (5), and eriosemaone A (27), were obtained by chemical synthesis for the first time. Key steps involved an electrocyclization to build the linear pyran rings and a Claisen/Cope rearrangement to install the 8-prenyl substituents. All compounds were assessed for their in vitro antimicrobial activities against clinically relevant human pathogens, including one Gram-negative bacterial strain (E. coli ATCC 25922) and four Gram-positive bacterial strains (S. aureus ATCC 29213, E. faecalis ATCC 29212, MRSA21-5, and VRE ATCC 51299). The result indicated that eriosemaone A (27) was the most potent one against Gram-positive bacteria, with minimum inhibitory concentrations in the range of 0.25-0.5 µg/mL. Mechanistic studies indicated that 27 has good membrane-targeting ability to bacterial inner membranes and can bind to phosphatidylglycerol and cardiolipin in bacterial membranes, thereby disrupting the bacterial cell membranes and causing bacterial death.

Survival outcomes and toxicity of adjuvant immunotherapy after definitive concurrent chemotherapy with proton beam radiation therapy for patients with inoperable locally advanced non-small cell lung carcinoma.

INTRODUCTION: Adjuvant immunotherapy (IO) following concurrent chemotherapy and photon radiation therapy confers an overall survival (OS) benefit for patients with inoperable locally advanced non-small cell lung carcinoma (LA-NSCLC); however, outcomes of adjuvant IO after concurrent chemotherapy with proton beam therapy (CPBT) are unknown. We investigated OS and toxicity after CPBT with adjuvant IO versus CPBT alone for inoperable LA-NSCLC. MATERIALS AND METHODS: We analyzed 354 patients with LA-NSCLC who were prospectively treated with CPBT with or without adjuvant IO from 2009 to 2021. Optimal variable ratio propensity score matching (PSM) matched CPBT with CPBT + IO patients. Survival was estimated with the Kaplan-Meier method and compared with log-rank tests. Multivariable Cox proportional hazards regression evaluated the effect of IO on disease outcomes. RESULTS: Median age was 70 years; 71 (20%) received CPBT + IO and 283 (80%) received CPBT only. After PSM, 71 CPBT patients were matched with 71 CPBT + IO patients. Three-year survival rates for CPBT + IO vs CPBT were: OS 67% vs 30% (P < 0.001) and PFS 59% vs 35% (P = 0.017). Three-year LRFS (P = 0.137) and DMFS (P = 0.086) did not differ. Receipt of adjuvant IO was a strong predictor of OS (HR 0.40, P = 0.001) and PFS (HR 0.56, P = 0.030), but not LRFS (HR 0.61, P = 0.121) or DMFS (HR 0.61, P = 0.136). There was an increased incidence of grade ≥3 esophagitis in the CPBT-only group (6% CPBT + IO vs 17% CPBT, P = 0.037). CONCLUSION: This study, one of the first to investigate CPBT followed by IO for inoperable LA-NSCLC, showed that IO conferred survival benefits with no increased rates of toxicity.

SPC25 Functions as a Prognostic-Related Biomarker, and Its High Expression Correlates with Tumor Immune Infiltration and UCEC Progression.

BACKGROUND: Most tumor tissues expressed spindle pole body component 25 (SPC25), one of the four subunits of the NDC80 complex, at greater levels compared to surrounding normal tissues. According to earlier researches, this subunit strongly encouraged tumor cell proliferation and tumor growth, which resulted in worse prognoses in patients with hepatocellular, breast, lung, and prostate cancer. Precisely because SPC25's role in uterine corpus endometrial carcinoma (UCEC) is understudied, we chose to concentrate on UCEC for gaining a more scientific and thorough understanding of SPC25. METHODS: Along with examining SPC25's differential expression, prognostic significance, and biological function in UCEC, our research sought to clarify the underlying mechanism by which SPC25 influences the course of UCEC and patient prognosis from the viewpoints of methylation and immune infiltration. RESULTS: We observed differential expression of SPC25 gene in different clinicopathological features of UCEC and identified SPC25 as a hazard factor for poorer overall survival (OS), disease-specific survival (DSS), and progress free interval (PFI) in UCEC, particularly in its multiple clinical subtypes. In addition, we also discovered that SPC25 and its co-expressed genes mostly engaged in biological processes and signal transduction routes linked to cell cycle and cell division in UCEC. After investigating SPC25's methylation status, we discovered that patients with UCEC had elevated SPC25 expression and a poor prognosis due to hypomethylation of CpG sites in the SPC25 gene sequence. Finally, we investigated SPC25's potential role in immunotherapy and discovered that SPC25 might alter the major immune cell infiltration levels in the tumor microenvironment (TME) by regulating the expression of immunoregulatory molecules and chemokines, which would be beneficial for SPC25 to control the progression of UCEC. CONCLUSIONS: In conclusion, SPC25 was a useful predictive biomarker as well as a possible therapeutic target for UCEC.