Three-dimensional printing the navigation template for precise percutaneous renal puncture to treat pyonephrosis on a porcine model and a patient ：a case report.

Objective: Percutaneous nephrolithotomy (PCNL) is the main method for pyonephrosis or lithotripsy in urology. However, it often comes with high risk, as the inaccurate puncture inevitably causes bleeding, intra- and post-operative complications. So, a new inter-disciplinary approach is needed to perform the puncture more accurately. Methods: 3 signs made of lead were marked onto the skin of the posterior side of the waist of a domestic pig or a patient, which was scanned by computed tomography (CT). Based on the CT images, the computer design and the 3D printing, a navigation template made of the transparent resin material is constructed. They were attached onto the surgical area on pig or patient according to the signs. During the PCNL, with this template, the puncture position, angle and depth were optimized in order to precisely enter the targeted renal pelvis or calices. Results: With the 3D navigation templates, 18G puncture needles were used to enter the renal pelvis upon performing the PCNL on a porcine model and a patient. On the porcine model, the urine outflow was observed with minimal complication. Post-operative CT scans revealed that the needle was located in the renal pelvis. For the patient case, the puncture point was designed to target the calix with stone. No obvious bleeding and complication was found in renal puncture with template. Conclusions: The navigation template was made with the combination of 3D printing, CT images and computer design. This template allows for accurate puncture of the renal pelvis or calix. Surgical improvement in kidney stones and pyonephrosis was observed in porcine model and patient case. In the future, prospective, trandomized, controlled clinical trials are needed to further confirm its advantage.

Identification of candidate genes associated with primary feathers of tianfu nonghua ducks based on Genome-wide association studies.

The primary feathers of ducks have important economic value in the poultry industry. This study quantified the primary feather phenotype of Nonghua ducks, including the primary feathers' length, area, distribution of black spots, and feather symmetry. And genome-wide association analysis was used to screen candidate genes that affect the primary feather traits. The genome-wide association study (GWAS) results identified the genetic region related to feather length (FL) on chromosome 2. Through Linkage disequilibrium (LD) analysis, candidate regions (chr2: 115,246,393-116,501,448 bp) were identified and were further annotated to 5 genes: MRS2, GPLD1, ALDH5A1, KIAA0319, and ATP9B. Secondly, candidate regions related to feather black spots were identified on chromosome 21. Through LD analysis, the candidate regions (chr21: 163,552-2,183,853 bp) were screened and further annotated to 47 genes. Among them, STK4, CCN5, and YWHAB genes were related to melanin-related pathways or pigment deposition, which may be key genes affecting the distribution of black spots on feathers. In addition, we also screened 125 genes on multiple chromosomes that may be related to feather symmetry. Among them, significant SNPs on chromosome 1 were further identified as candidate regions (chr1: 142,118,209-142,223,605 bp) through LD analysis and annotated into 2 genes, TGFBRAP1 and LOC113839965. These results reported the genetic basis of the primary feather from multiple phenotypes, and offered valuable insights into the genetic basis for the growth and development of duck feathers and feather color pattern.

Palladium-Catalyzed Enantioselective Multicomponent Cross-Coupling of Trisubstituted Olefins.

The development of a catalytic method for stereogenic carbon center formation holds immense significance in organic synthesis. Transition-metal-catalyzed cross-coupling reaction has been regarded as a straightforward and efficient tool for stereoselectively forging C-C bond. Nevertheless, the creation of acyclic all-carbon quaternary-containing vicinal stereocenters remains notoriously challenging within the domain of cross-coupling chemistry despite their prominence in various bioactive small molecules. Herein, we describe a palladium-catalyzed asymmetric multicomponent cross-coupling of trisubstituted alkene with aryl diazonium salts and arylboronic acids to realize the formation of tertiary-quaternary carbon centers with high regio-, distereo-, and enantioselectivity. Specifically, the precise manipulation of the stereoconfiguration of trisubstituted alkenes enables the divergent stereoselective cross-coupling reaction, thus allowing for the facile construction of all four enantiomers. Harnessing the ligand-swap strategy involving a chiral bisoxazoline and an achiral fumarate individually accelerates the enantioselective migratory insertion and reductive elimination step in the cross-coupling process, as supported by density functional theory (DFT) calculations, thus obviating the requirement for a neighboring directing group within the internal olefin skeleton.

Advances in bacteria-based drug delivery systems for anti-tumor therapy.

In recent years, bacteria have gained considerable attention as a promising drug carrier that is critical in improving the effectiveness and reducing the side effects of anti-tumor drugs. Drug carriers can be utilised in various forms, including magnetotactic bacteria, bacterial biohybrids, minicells, bacterial ghosts and bacterial spores. Additionally, functionalised and engineered bacteria obtained through gene engineering and surface modification could provide enhanced capabilities for drug delivery. This review summarises the current studies on bacteria-based drug delivery systems for anti-tumor therapy and discusses the prospects and challenges of bacteria as drug carriers. Furthermore, our findings aim to provide new directions and guidance for the research on bacteria-based drug systems.

Follicular CD8+ T cells promote immunoglobulin production and demyelination in multiple sclerosis and a murine model.

Emerging evidence underscores the importance of CD8+ T cells in the pathogenesis of multiple sclerosis (MS), but the precise mechanisms remain ambiguous. This study intends to elucidate the involvement of a novel subset of follicular CD8+ T cells (CD8+CXCR5+ T) in MS and an experimental autoimmune encephalomyelitis (EAE) murine model. The expansion of CD8+CXCR5+ T cells was observed in both MS patients and EAE mice during the acute phase. In relapsing MS patients, higher frequencies of circulating CD8+CXCR5+ T cells were positively correlated with new gadolinium-enhancement lesions in the central nervous system (CNS). In EAE mice, frequencies of CD8+CXCR5+ T cells were also positively correlated with clinical scores. These cells were found to infiltrate into ectopic lymphoid-like structures in the spinal cords during the peak of the disease. Furthermore, CD8+CXCR5+ T cells, exhibiting high expression levels of ICOS, CD40L, IL-21, and IL-6, were shown to facilitate B cell activation and differentiation through a synergistic interaction between CD40L and IL-21. Transferring CD8+CXCR5+ T cells into naïve mice confirmed their ability to enhance the production of anti-MOG35-55 antibodies and contribute to the disease progression. Consequently, CD8+CXCR5+ T cells may play a role in CNS demyelination through heightening humoral immune responses.

HMGA2 promotes resistance against paclitaxel by targeting the p53 signaling pathway in colorectal cancer cells.

Colorectal cancer is one of the most common malignancies and ranks second in terms of cancer-related mortality worldwide due to its metastasis, drug resistance, and reoccurrence. High-mobility gene group A2 (HMGA2) is overexpressed in colorectal cancer, contributing to the aggressiveness of tumor malignance, and promotes drug resistance in many types of cancer. However, the underlying molecular mechanism of HMGA2 is yet to be elucidated. In this study, we showed that HMGA2 is overexpressed in colorectal cancer tissue, and knockdown of HMGA2 significantly inhibited colorectal cancer cell growth and migratory capability. HMGA2 regulates the cancer cell response to a widely used anti-cancer drug, paclitaxel (PTX). HMGA2 knockdown increased cell death, whereas HMGA2 overexpression decreased cell death after PTX treatment. Furthermore, lower reactive oxygen species (ROS) levels and mitochondrial potential were detected in HMGA2 overexpression cells after PTX treatment. However, HMGA2 knockdown produced the opposite effect. RNA sequencing showed a p53 signaling pathway-dependent regulation in HMGA2 knockdown cells. Combined with p53 inhibitors and HMGA2 knockdown, a synergetic effect of more cell death was observed in colorectal cancer cells after PTX treatment. Thus, we showed that HMGA2 can activate p53 signaling to regulate colorectal cancer cell death after PTX treatment. Altogether, our results reveal novel insights into the molecular mechanisms underlying HMGA2-mediated cancer cell resistance against PTX and highlight the potential of targeting HMGA2 and p53 signaling for the therapeutic investigation of colorectal cancer.

Efficacy of angiotensin receptor blockers for nocturnal blood pressure reduction: a systematic review and meta-analysis.

BACKGROUND: Nocturnal blood pressure (BP) is correlated with an increased risk of cardiovascular events and is an important predictor of cardiovascular death in hypertensive patients. OBJECTIVE: Nocturnal BP control is of great importance for cardiovascular risk reduction. This systematic review and meta-analysis aimed to explore the efficacy of angiotensin receptor blockers (ARBs) for nocturnal BP reduction in patients with mild to moderate hypertension. METHODS: PICOS design structure was used to formulate the data extraction. All statistical calculations and analyses were performed with R. RESULTS: Seventy-seven studies with 13,314 participants were included. The overall analysis indicated that nocturnal BP drop varied considerably among different ARBs. Allisartan (13.04 [95% CI (-18.41, -7.68)] mmHg), olmesartan (11.67 [95% CI (-14.12, -9.21)] mmHg), telmisartan (11.11 [95% CI (-12.12, -10.11)] mmHg) were associated with greater reduction in nocturnal systolic BP. In the aspect of the nocturnal-diurnal BP drop ratio, only allisartan was greater than 1. While, the variation tendency of last 4-6 h ambulatory BP was basically consistent with nocturnal BP. Additionally, allisartan showed improvement effect in the proportion of patients with dipping BP pattern. CONCLUSIONS: This study demonstrates that for patients with mild to moderate hypertension, allisartan, olmesartan and telmisartan have more advantages in nocturnal BP reduction among the ARBs, while allisartan can reduce nighttime BP more than daytime BP and improve the dipping pattern.

This meta-analysis explores the efficacy of Angiotensin II AT1 receptor antagonists (ARBs) on nocturnal blood pressure (BP) reduction in mild to moderate hypertension.The results demonstrate that for patients with mild to moderate hypertension, allisartan, olmesartan and telmisartan have more advantages in nocturnal BP reduction among the ARBs.Allisartan can reduce nighttime BP more effectively than daytime BP, which also improve the dipping pattern.

Genome-wide association analysis explores the genetic loci of amino acid content in duck's breast muscle.

BACKGROUND: Amino acids are the basic components of protein and an important index to evaluate meat quality. With the rapid development of genomics, candidate regions and genes affecting amino acid content in livestock and poultry have been gradually revealed. Hence, genome-wide association study (GWAS) can be used to screen candidate loci associated with amino acid content in duck meat. RESULT: In the current study, the content of 16 amino acids was detected in 358 duck breast muscles. The proportion of Glu to the total amino acid content was relatively high, and the proportion was 0.14. However, the proportion of Met content was relatively low, at just 0.03. By comparative analysis, significant differences were found between males and females in 3 amino acids, including Ser, Met, and Phe. In addition, 12 SNPs were significantly correlated with Pro content by GWAS analysis, and these SNPs were annotated by 7 protein-coding genes; 8 significant SNPs were associated with Tyr content, and these SNPs were annotated by 6 protein-coding genes. At the same time, linkage disequilibrium (LD) analysis was performed on these regions with significant signals. The results showed that three SNPs in the 55-56 Mbp region of chromosome 3 were highly correlated with the leader SNP (chr3:55526954) that affected Pro content (r2 > 0.6). Similarly, LD analysis showed that there were three SNPs in the 21.2-21.6 Mbp region of chromosome 13, which were highly correlated with leader SNP (chr13:21421661) (r2 > 0.6). Moreover, Through functional enrichment analysis of all candidate genes. The results of GO enrichment analysis showed that several significant GO items were associated with amino acid transport function, including amino acid transmembrane transport and glutamine transport. The results further indicate that these candidate genes are closely associated with amino acid transport. Among them, key candidate genes include SLC38A1. For KEGG enrichment analysis, CACNA2D3 and CACNA1D genes were covered by significant pathways. CONCLUSION: In this study, GWAS analysis found a total of 28 significant SNPs affecting amino acid content. Through gene annotation, a total of 20 candidate genes were screened. In addition, Through LD analysis and enrichment analysis, we considered that SERAC1, CACNA2D3 and SLC38A1 genes are important candidate genes affecting amino acid content in duck breast muscle.

Covalent targeted radioligands potentiate radionuclide therapy.

Targeted radionuclide therapy, in which radiopharmaceuticals deliver potent radionuclides to tumours for localized irradiation, has addressed unmet clinical needs and improved outcomes for patients with cancer1-4. A therapeutic radiopharmaceutical must achieve both sustainable tumour targeting and fast clearance from healthy tissue, which remains a major challenge5,6. A targeted ligation strategy that selectively fixes the radiopharmaceutical to the target protein in the tumour would be an ideal solution. Here we installed a sulfur (VI) fluoride exchange (SuFEx) chemistry-based linker on radiopharmaceuticals to prevent excessively fast tumour clearance. When the engineered radiopharmaceutical binds to the tumour-specific protein, the system undergoes a binding-to-ligation transition and readily conjugates to the tyrosine residues through the 'click' SuFEx reaction. The application of this strategy to a fibroblast activation protein (FAP) inhibitor (FAPI) triggered more than 80% covalent binding to the protein and almost no dissociation for six days. In mice, SuFEx-engineered FAPI showed 257% greater tumour uptake than did the original FAPI, and increased tumour retention by 13-fold. The uptake in healthy tissues was rapidly cleared. In a pilot imaging study, this strategy identified more tumour lesions in patients with cancer than did other methods. SuFEx-engineered FAPI also successfully achieved targeted ß- and α-radionuclide therapy, causing nearly complete tumour regression in mice. Another SuFEx-engineered radioligand that targets prostate-specific membrane antigen (PSMA) also showed enhanced therapeutic efficacy. Considering the broad scope of proteins that can potentially be ligated to SuFEx warheads, it might be possible to adapt this strategy to other cancer targets.

Unlocking the power of Zc3h12c: Orchestrating Macrophage activation and elevating the innate immune response.

The activation of macrophages, essential for the innate defense against invading pathogens, revolves around Toll-like receptors (TLRs). Nevertheless, a comprehensive understanding of the molecular mechanisms governing TLR signaling in the course of macrophage activation remains to be fully clarified. Although Zc3h12c was originally identified as being enriched in organs associated with macrophages, its precise function remains elusive. In this study, we observed a significant induction of Zc3h12c in macrophages following stimulation with TLR agonists and pathogens. Overexpression of Zc3h12c significantly mitigated the release of TNF-α and IL-6 triggered by lipopolysaccharide (LPS), whereas depletion of Zc3h12c increased the production of the cytokines mentioned above. Notably, the expression of IFN-ß was not influenced by Zc3h12c. Luciferase reporter assays revealed that Zc3h12c could suppress the TNF-α promoter activity. Moreover, Zc3h12c exerted a notable inhibitory effect on JNK, ERK, p38, and NF-κB signaling induced by LPS. In summary, the findings of our study suggest that Zc3h12c functions as a robust suppressor of innate immunity, potentially playing a role in the pathogenesis of infectious diseases.

Naringenin relieves paclitaxel-induced pain by suppressing calcitonin gene-related peptide signalling and enhances the anti-tumour action of paclitaxel.

BACKGROUND AND PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) commonly causes neuropathic pain, but its pathogenesis remains unclear, and effective therapies are lacking. Naringenin, a natural dihydroflavonoid compound, has anti-inflammatory, anti-nociceptive and anti-tumour activities. However, the effects of naringenin on chemotherapy-induced pain and chemotherapy effectiveness remain unexplored. EXPERIMENTAL APPROACH: Female and male mouse models of chemotherapy-induced pain were established using paclitaxel. Effects of naringenin were assessed on pain induced by paclitaxel or calcitonin gene-related peptide (CGRP) and on CGRP expression in dorsal root ganglia (DRG) and spinal cord tissue. Additionally, we examined peripheral macrophage infiltration, glial activation, c-fos expression, DRG neuron excitability, microglial M1/M2 polarization, and phosphorylation of spinal NF-κB. Furthermore, we investigated the synergic effect and related mechanisms of naringenin and paclitaxel on cell survival of cancer cells in vitro. KEY RESULTS: Systemic administration of naringenin attenuated paclitaxel-induced pain in both sexes. Naringenin reduced paclitaxel-enhanced CGRP expression in DRGs and the spinal cord, and alleviated CGRP-induced pain in naïve mice of both sexes. Naringenin mitigated macrophage infiltration and reversed paclitaxel-elevated c-fos expression and DRG neuron excitability. Naringenin decreased spinal glial activation and NF-κB phosphorylation in both sexes but influenced microglial M1/M2 polarization only in females. Co-administration of naringenin with paclitaxel enhanced paclitaxel's anti-tumour effect, impeded by an apoptosis inhibitor. CONCLUSION AND IMPLICATIONS: Naringenin's anti-nociceptive mechanism involves CGRP signalling and neuroimmunoregulation. Furthermore, naringenin facilitates paclitaxel's anti-tumour action, possibly involving apoptosis. This study demonstrates naringenin's potential as a supplementary treatment in cancer therapy by mitigating side effects and potentiating efficacy of chemotherapy.

Role of pyroptosis-related cytokines in the prediction of lung cancer.

Objectives: Lung cancer is the leading cause to induce cancer-related mortality. Effective biomarkers for prediction the occurrence of lung cancer is urgently needed. Our previous studies indicated that pyroptosis-related cytokines TNF-α, IFN-γ, MIP-1α, MIP-1ß, MIP-2 and IP-10 is important to influence the efficacy of chemotherapy drug in lung cancer tissues. But the role of pyroptosis-related cytokines in prediction the occurrence of lung cancer is still unknown. Methods: Blood samples were collected from 258 lung cancer patients at different stage and 80 healthy volunteers. Serum levels of pyroptosis-related cytokines including TNF-α, IFN-γ, MIP-1α, MIP-1ß, MIP-2 and IP-10 were measured by Cytometric Bead Array (CBA). ROC curve was performed to evaluate the cut-off value and diagnosis value for prediction and diagnosis of lung cancer. Results: Compared with control group, the levels of IP-10, MIP-1α, MIP-1ß, MIP-2 and TNF-α were significantly higher in lung cancer patients (45.5 (37.1-56.7): 57.2 (43.0-76.5), 34.4 (21.8-75.2): 115.4 (96.6-191.2), 49.3 (25.6-78.7): 160.5 (124.9-218.6), 22.6 (17.8-31.2): 77.9 (50.1-186.5), 3.80 (2.3-6.2): 10.3 (5.7-16.6)), but the level of IFN-γ was decreased in the patients (12.38 (9.1-27.8): 5.9 (3.5-9.7)). All the above cytokines were significantly associated with the diagnosis of lung cancer, and the AUC values of IFN-γ, IP-10, MIP-1α, MIP-1ß, MIP-2, and TNF-α were 0.800, 0.656, 0.905, 0.921, 0.914, and 0.824. And the AUC can rise to 0.986 after combining the above factors, and the sensitivity and specificity also up to 96.7 % and 93.7 %, respectively. Additionally, TNF-α (r = 0.400, P < 0.01), MIP-2 (r = 0.343, P < 0.01), MIP-1α (r = 0.551, P < 0.01) and MIP-1ß (r = 0.403, p < 0.01) were positively associated with occurrence of lung cancer, but IFN-γ (r = -0.483, p < 0.01) was negatively associated with occurrence of lung cancer. As far as the potential of early diagnosis of lung cancer, TNF-α (AUC = 0.577), MIP-1α (AUC = 0.804) and MIP-1ß (AUC = 0.791) can predict the early stage of lung cancer, and combination of the above three cytokines has a better predictive efficiency (AUC = 0.854). Conclusion: Our study establishes a link between the levels of IP-10, MIP-1α, MIP-1ß, MIP-2, TNF-α and IFN-γ and diagnosis of lung cancer. Besides, we observed a synergistic effect of these five pyroptosis-related cytokines in diagnosing lung cancer patient, suggesting their potential as biomarkers for lung cancer diagnosis. Moreover, the combination of TNF-α, MIP-1α and MIP-1ß are also potential predictors for the early diagnosis of lung cancer.

Theoretical Perspective on the Design of Surface Frustrated Lewis Pairs for Small-Molecule Activation.

The excellent reactivity of frustrated Lewis pairs (FLP) to activate small molecules has gained increasing attention in recent decades. Though the development of surface FLP (SFLP) is prompting the application of FLP in the chemical industry, the design of SFLP with superior activity, high density, and excellent stability for small-molecule activation is still challenging. Herein, we review the progress of designing SFLP by surface engineering, screening natural SFLP, and the dynamic formation of SFLP from theoretical perspectives. We highlight the breakthrough in fine-tuning the activity, density, and stability of the designed SFLP studied by using computational methods. We also discuss future challenges and directions in designing SFLP with outstanding capabilities for small-molecule activation.

Role of oxidative stress-induced ferroptosis in cancer therapy.

Ferroptosis is a distinct mode of cell death, distinguishing itself from typical apoptosis by its reliance on the accumulation of iron ions and lipid peroxides. Cells manifest an imbalance between oxidative stress and antioxidant equilibrium during certain pathological contexts, such as tumours, resulting in oxidative stress. Notably, recent investigations propose that heightened intracellular reactive oxygen species (ROS) due to oxidative stress can heighten cellular susceptibility to ferroptosis inducers or expedite the onset of ferroptosis. Consequently, comprehending role of ROS in the initiation of ferroptosis has significance in elucidating disorders related to oxidative stress. Moreover, an exhaustive exploration into the mechanism and control of ferroptosis might offer novel targets for addressing specific tumour types. Within this context, our review delves into recent fundamental pathways and the molecular foundation of ferroptosis. Four classical ferroptotic molecular pathways are well characterized, namely, glutathione peroxidase 4-centred molecular pathway, nuclear factor erythroid 2-related factor 2 molecular pathway, mitochondrial molecular pathway, and mTOR-dependent autophagy pathway. Furthermore, we seek to elucidate the regulatory contributions enacted by ROS. Additionally, we provide an overview of targeted medications targeting four molecular pathways implicated in ferroptosis and their potential clinical applications. Here, we review the role of ROS and oxidative stress in ferroptosis, and we discuss opportunities to use ferroptosis as a new strategy for cancer therapy and point out the current challenges persisting within the domain of ROS-regulated anticancer drug research and development.

The complete chloroplast genome sequence of Zanthoxylum ailanthoides Sieb. et. Zucc (Rutaceae): an important medicinal plant.

Zanthoxylum ailanthoides is a deciduous tree, with important medicinal and economic values. The complete chloroplast genome sequence of Z. ailanthoides was assembled and the phylogenetic relationship to other species was inferred in this study. The chloroplast genome is 157,209 bp in length, including two inverted repeats of 26,408 bp, a large single-copy of 86,099 bp and a small single copy of 18,294 bp. Moreover, the chloroplast genome contains 129 genes, including 84 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The overall GC content of the chloroplast genome is 38.4%. The phylogenetic analysis indicated that Z. ailanthoides was grouped with a clade containing the species of Z. multijugum, Z. calcicola, Z. oxyphyllum, Z. stenophyllum, and the genus was closely related to Phellodendron. This study contributes to a better understanding of the phylogenetic relationships among Zanthoxylum species.

Light-Chain Cardiac Amyloidosis: Cardiac Magnetic Resonance for Assessing Response to Chemotherapy.

OBJECTIVE: Cardiac magnetic resonance (CMR) is a diagnostic tool that provides precise and reproducible information about cardiac structure, function, and tissue characterization, aiding in the monitoring of chemotherapy response in patients with light-chain cardiac amyloidosis (AL-CA). This study aimed to evaluate the feasibility of CMR in monitoring responses to chemotherapy in patients with AL-CA. MATERIALS AND METHODS: In this prospective study, we enrolled 111 patients with AL-CA (50.5% male; median age, 54 [interquartile range, 49-63] years). Patients underwent longitudinal monitoring using biomarkers and CMR imaging. At follow-up after chemotherapy, patients were categorized into superior and inferior response groups based on their hematological and cardiac laboratory responses to chemotherapy. Changes in CMR findings across therapies and differences between response groups were analyzed. RESULTS: Following chemotherapy (before vs. after), there were significant increases in myocardial T2 (43.6 ± 3.5 ms vs. 44.6 ± 4.1 ms; P = 0.008), recovery in right ventricular (RV) longitudinal strain (median of -9.6% vs. -11.7%; P = 0.031), and decrease in RV extracellular volume fraction (ECV) (median of 53.9% vs. 51.6%; P = 0.048). These changes were more pronounced in the superior-response group. Patients with superior cardiac laboratory response showed significantly greater reductions in RV ECV (-2.9% [interquartile range, -8.7%-1.1%] vs. 1.7% [-5.5%-7.1%]; P = 0.017) and left ventricular ECV (-2.0% [-6.0%-1.3%] vs. 2.0% [-3.0%-5.0%]; P = 0.01) compared with those with inferior response. CONCLUSION: Cardiac amyloid deposition can regress following chemotherapy in patients with AL-CA, particularly showing more prominent regression, possibly earlier, in the RV. CMR emerges as an effective tool for monitoring associated tissue characteristics and ventricular functional recovery in patients with AL-CA undergoing chemotherapy, thereby supporting its utility in treatment response assessment.

Rev1 overexpression accelerates N-methyl-N-nitrosourea (MNU)-induced thymic lymphoma by increasing mutagenesis.

Rev1 has two important functions in the translesion synthesis pathway, including dCMP transferase activity, and acts as a scaffolding protein for other polymerases involved in translesion synthesis. However, the role of Rev1 in mutagenesis and tumorigenesis in vivo remains unclear. We previously generated Rev1-overexpressing (Rev1-Tg) mice and reported that they exhibited a significantly increased incidence of intestinal adenoma and thymic lymphoma (TL) after N-methyl-N-nitrosourea (MNU) treatment. In this study, we investigated mutagenesis of MNU-induced TL tumorigenesis in wild-type (WT) and Rev1-Tg mice using diverse approaches, including whole-exome sequencing (WES). In Rev1-Tg TLs, the mutation frequency was higher than that in WT TL in most cases. However, no difference in the number of nonsynonymous mutations in the Catalogue of Somatic Mutations in Cancer (COSMIC) genes was observed, and mutations involved in Notch1 and MAPK signaling were similarly detected in both TLs. Mutational signature analysis of WT and Rev1-Tg TLs revealed cosine similarity with COSMIC mutational SBS5 (aging-related) and SBS11 (alkylation-related). Interestingly, the total number of mutations, but not the genotypes of WT and Rev1-Tg, was positively correlated with the relative contribution of SBS5 in individual TLs, suggesting that genetic instability could be accelerated in Rev1-Tg TLs. Finally, we demonstrated that preleukemic cells could be detected earlier in Rev1-Tg mice than in WT mice, following MNU treatment. In conclusion, Rev1 overexpression accelerates mutagenesis and increases the incidence of MNU-induced TL by shortening the latency period, which may be associated with more frequent DNA damage-induced genetic instability.

The complete chloroplast genome of Hemiboea pterocaulis (Gesneriaceae) exclusively distributed in Guilin, Guangxi, China.

Hemiboea pterocaulis is a unique species only found in Guilin, Guangxi, China. In this study, we sequenced and assembled the complete chloroplast genome of H. pterocaulis and revealed its phylogenetic relationship with other Hemiboea species. The chloroplast genome sequence of H. pterocaulis is 153,159 bp in length and comprises a large single-copy (LSC) region of 84,178 bp, a small single-copy (SSC) region of 18,087 bp, and a pair of inverted repeat (IR) regions, each with a length of 25,447 bp. It has a total GC content of 37.6% and encodes 132 genes, including 87 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The phylogenetic relationships based on the complete chloroplast genome sequences of Hemiboea taxa indicate that H. pterocaulis is most closely related to H. suiyangensis, indicating that H. pterocaulis is an independent species and is separated from the H. subcapitata complex. These results provide valuable insights into the phylogeny, species divergence, and delimitation of the Hemiboea genus.

Key chromatin regulator-related genes associated with the risk of coronary artery disease regulate the expression of HCFC1, RNF8, TNP1 and SET.

Chromatin regulators are indispensable upstream epigenetic regulators.The emergence and progression of atherosclerosis has been demonstrated to be influenced by smooth muscle-related chromatin regulators, such as ZEB2 and MAFF. However, specific chromatin regulators and their possible roles have not been clarified. Information was gathered from 51 patients diagnosed with coronary artery disease (CAD) and 50 individuals in good health from the GEO database. 440 genes were identified as having differential expression across the two datasets, and these genes were linked to cellular reactions. Enrichment of pathways related to histone modification and transcriptional regulatory factors was observed in GO and KEGG analyses. Four machine learning models (RF, SVM, GLM, and XGB) were developed using the expression profiles of 440 chromatin-associated genes in the CAD cohort to pinpoint genes with significant diagnostic potential. After evaluating residuals, root mean square errors, receiver operating characteristic curves, and immune-infiltration, four key genes (HCFC1, RNF8, TNP1, and SET) were identified. Gene expression in different blood vessel levels in atherosclerotic plaques in a mouse model of coronary artery disease showed significant variations. The gene expression levels in macrophages aligned with clinical data from the GEO database as expected. This discovery is crucial for future analysis and the prediction of drug and miRNA targets. In conclusion, we found that the four hub genes are important in the mechanism of CAD. These findings provide new ideas for the study of potential epigenetic predictive markers and therapeutic targets to be used in determining a treatment strategy for CAD.

Finding Natural, Dense, and Stable Frustrated Lewis Pairs on Wurtzite Crystal Surfaces for Small-Molecule Activation.

The surface frustrated Lewis pairs (SFLPs) open up new opportunities for substituting noble metals in the activation and conversion of stable molecules. However, the applications of SFLPs on a larger scale are impeded by the complex construction process, low surface density, and sensitivity to the reaction environment. Herein, wurtzite-structured crystals such as GaN, ZnO, and AlP are found for developing natural, dense, and stable SFLPs. It is revealed that the SFLPs can naturally exist on the (100) and (110) surfaces of wurtzite-structured crystals. All the surface cations and anions serve as the Lewis acid and Lewis base in SFLPs, respectively, contributing to the surface density of SFLPs as high as 7.26×1014 cm-2. Ab initio molecular dynamics simulations indicate that the SFLPs can keep stable under high temperatures and the reaction atmospheres of CO and H2O. Moreover, outstanding performance for activating the given small molecules is achieved on these natural SFLPs, which originates from the optimal orbital overlap between SFLPs and small molecules. Overall, these findings not only provide a simple method to obtain dense and stable SFLPs but also unfold the nature of SFLPs toward the facile activation of small molecules.