Consensus clustering and development of a risk signature based on trajectory differential genes of cancer-associated fibroblast subpopulations in colorectal cancer.

BACKGROUND: Cancer-associated fibroblasts (CAFs) play a crucial role in the progression of colorectal cancer (CRC). However, the impact of CAF subpopulation trajectory differentiation on CRC remains unclear. METHODS: In this study, we first explored the trajectory differences of CAFs subpopulations using bulk and integrated single-cell sequencing data, and then performed consensus clustering of CRC samples based on the trajectory differential genes of CAFs subpopulations. Subsequently, we analyzed the heterogeneity of CRC subtypes using bioinformatics. Finally, we constructed relevant prognostic signature using machine learning and validated them using spatial transcriptomic data. RESULTS: Based on the differential genes of CAFs subpopulation trajectory differentiation, we identified two CRC subtypes (C1 and C2) in this study. Compared to C1, C2 exhibited worse prognosis, higher immune evasion microenvironment and high CAF characteristics. C1 was primarily associated with metabolism, while C2 was primarily associated with cell metastasis and immune regulation. By combining 101 combinations of 10 machine learning algorithms, we developed a High-CAF risk signatures (HCAFRS) based on the C2 characteristic gene. HCAFRS was an independent prognostic factor for CRC and, when combined with clinical parameters, significantly predicted the overall survival of CRC patients. HCAFRS was closely associated with epithelial-mesenchymal transition, angiogenesis, and hypoxia. Furthermore, the risk score of HCAFRS was mainly derived from CAFs and was validated in the spatial transcriptomic data. CONCLUSION: In conclusion, HCAFRS has the potential to serve as a promising prognostic indicator for CRC, improving the quality of life for CRC patients.

Manganese-catalyzed cyclopropanation of allylic alcohols with sulfones.

Cyclopropanes are among the most important structural units in natural products, pharmaceuticals, and agrochemicals. Herein, we report a manganese-catalyzed cyclopropanation of allylic alcohols with sulfones as carbene alternative precursors via a borrowing hydrogen strategy under mild conditions. Various allylic alcohols and arylmethyl trifluoromethyl sulfones work efficiently in this borrowing hydrogen transformation and thereby deliver the corresponding cyclopropylmethanol products in 58% to 99% yields. Importantly, a major benefit of this transformation is that the versatile free alcohol moiety is retained in the resultant products, which can undergo a wide range of downstream transformations to provide access to a series of functional molecules. Mechanistic studies support a sequential reaction mechanism that involves catalytic dehydrogenation, Michael addition, cyclization, and catalytic hydrogenation.

A temperature-compensated CO2 detection system based on non-dispersive infrared spectral technology.

The concentration of carbon dioxide (CO2) is an important indicator for coal mine safety. Real-time monitoring of CO2 concentration is of great importance for taking actions in advance to avoid the occurrence of potential accidents. To address the issues of poor portability and high cost associated with existing coal mine CO2 detection equipment, this paper develops a miniaturized CO2 detection system based on non-dispersive infrared (NDIR) technology. This sensor integrates an infrared light source and a dual-channel pyroelectric detector into a reflective gas chamber, thereby achieving an extended optical path and higher system sensitivity within limited space. Meanwhile, the noise interference was greatly mitigated by using hardware and software filtering techniques. Based on principle analysis, the Lambert-Beer law was parametrically corrected, and then, a model relationship between the dual-channel voltage ratio and concentration was established. In addition, temperature compensation for zero and span values was introduced to improve the adaptability of the detection results to temperature changes. Testing results indicate that the developed detection system can realize CO2 measurement in the concentration range of 0 to 50 000 ppm within a temperature range of 0-40 °C, with a maximum detection error of less than 0.12% and a repeatability deviation of less than 1.04%. During a stability test for 12 h, the maximum concentration drift is 0.07%, indicating that the developed system meets the requirements for monitoring CO2 safety in coal mines.

Comparison of ovarian preservation versus oophorectomy on fertility outcomes in patients with endometriosis post-laparoscopic surgery: A prospective study.

BACKGROUND: Endometriosis is a chronic inflammatory condition affecting a significant proportion of women of reproductive age. Although laparoscopic surgery is commonly the preferred treatment, the decision to preserve or remove the ovaries remains controversial. Previous studies have yielded inconsistent results regarding the impact of ovarian preservation vs oophorectomy on fertility outcomes and disease recurrence. This prospective study aimed to address this knowledge gap by comparing the effects of these surgical approaches on spontaneous pregnancy rates, time to pregnancy, recurrence rates, and postoperative pain in patients with endometriosis. AIM: To compare the reproductive outcomes and recurrence rates between ovarian preservation and oophorectomy in women undergoing laparoscopic surgery for endometriosis. METHODS: This study was conducted at a tertiary care hospital between January 2019 and December 2023. A total of 312 women aged 18 to 40 years, diagnosed with endometriosis and undergoing laparoscopic surgery, were included. The patients were categorized into the ovarian preservation group (n = 204) and the oophorectomy group (n = 108). The primary outcome measure was the achievement of spontaneous pregnancy within 24 months post-surgery. Secondary outcomes included time to spontaneous pregnancy, recurrence rates, and postoperative pain scores. RESULTS: The ovarian preservation group exhibited a significantly higher spontaneous pregnancy rate than that in the oophorectomy group (43.6% vs 28.7%, P = 0.006). Moreover, the median time to spontaneous pregnancy was shorter in the ovarian preservation group (8.2 months vs 11.4 months, P = 0.018). Nonetheless, endometriosis recurrence was more prevalent in the ovarian preservation group (22.1% vs 11.1%, P = 0.014). The postoperative pain scores demonstrated similar improvements in both groups, with no significant differences observed. Subgroup analyses indicated that the benefit of ovarian preservation on spontaneous pregnancy rates was more evident among younger women (≤ 35 years) and those with advanced-stage endometriosis. CONCLUSION: Ovarian preservation is associated with a high spontaneous pregnancy rate and a short time to pregnancy. However, because of the increased risk of recurrence, the decision should be based on age, fertility aspirations, and disease severity.

Large scale exploration reveals rare taxa crucially shape microbial assembly in alkaline lake sediments.

Alkaline lakes are extreme environments inhabited by diverse microbial extremophiles. However, large-scale distribution patterns, environmental adaptations, community assembly, and evolutionary dynamics of microbial communities remain largely underexplored. This study investigated the characteristics of microbial communities on rare and abundant taxa in alkaline lake sediments in west and northwest China. We observed that abundant taxa varied significantly with geographical distance, while rare taxa remained unaffected by regional differences. The assembly process of abundant taxa was influenced by dispersal limitation, whilst rare taxa were predominantly driven by heterogeneous selection. Network analysis indicated that rare taxa as core species for community interactions and community stability. Rare taxa exhibited higher speciation and transition rate than abundant taxa, serving as a genetic reservoir and potential candidates to become abundance taxa, highlighting their crucial role in maintaining microbial diversity. These insights underscore the significant influence of rare taxa on ecosystem biodiversity and stability in alkaline lakes.

Sirt6 overexpression relieves ferroptosis and delays the progression of diabetic nephropathy via Nrf2/GPX4 pathway.

OBJECTIVE: Sirt6, reactive oxygen species and ferroptosis may participate in the pathogenesis of Diabetic Nephropathy (DN). Exploring the relationship between Sirt6, oxidative stress, and ferroptosis provides new scientific ideas to DN. METHODS: Human podocytes were stimulated with 30 mM glucose and 5.5 mM glucose. The mice of db/db group were randomly divided into two groups:12 weeks and 16 weeks. Collect mouse blood and urine specimens and renal cortices for investigations. HE, Masson, PAS and immunohistochemical staining were used to observe pathological changes. Western blot, RT-qPCR and immunofluorescence staining were used to evaluate expression of relevant molecules. CCK8 method was introduced to observe cell viability. The changes of podocyte mitochondrial membrane potential and mitochondrial morphology in each group were determined by JC-1 staining and Mito-Tracker. RESULTS: The expression level of Sirt6, Nrf2, SLC7A11, HO1, SOD2 and GPX4 were reduced, while ACSL4 was increased in DN. Blood glucose, BUN, Scr, TG, T-CHO and 24h urine protein were upregulated, while ALB was reduced in diabetic group. The treatment of Ferrostatin-1 significantly improved these changes, which proved ferroptosis was involved in the development of DN. Overexpression of Sirt6 might ameliorate the oxidation irritable reaction and ferroptosis. Sirt6 plasmid transfection increased mitochondrial membrane potential and protected morphology and structure of mitochondria. The application of Sirt6 siRNA could aggravated the damage manifestations. CONCLUSION: High glucose stimulation could decrease the antioxidant capacity and increase formation of ROS and lipid peroxidation. Sirt6 might alleviate HG-induced mitochondrial dysfunction, podocyte injury and ferroptosis through regulating Nrf2/GPX4 pathway.

Spatiotemporal Variations in Co-Occurrence Patterns of Planktonic Prokaryotic Microorganisms along the Yangtze River.

Bacteria and archaea are foundational life forms on Earth and play crucial roles in the development of our planet's biological hierarchy. Their interactions influence various aspects of life, including eukaryotic cell biology, molecular biology, and ecological dynamics. However, the coexistence network patterns of these microorganisms within natural river ecosystems, vital for nutrient cycling and environmental health, are not well understood. To address this knowledge gap, we systematically explored the non-random coexistence patterns of planktonic bacteria and archaea in the 6000-km stretch of the Yangtze River by using high-throughput sequencing technology. By analyzing the O/R ratio, representing the divergence between observed (O%) and random (R%) co-existence incidences, and the module composition, we found a preference of both bacteria and archaea for intradomain associations over interdomain associations. Seasons notably influenced the co-existence of bacteria and archaea, and archaea played a more crucial role in spring as evidenced by their predominant presence of interphyla co-existence and more species as keystone ones. The autumn network was characterized by a higher node or edge number, greater graph density, node degree, degree centralization, and nearest neighbor degree, indicating a more complex and interconnected structure. Landforms markedly affected microbial associations, with more complex networks and more core species found in plain and non-source areas. Distance-decay analysis suggested the importance of geographical distance in shaping bacteria and archaea co-existence patterns (more pronounced in spring). Natural, nutrient, and metal factors, including water temperature, NH4+-N, Fe, Al, and Ni were identified as crucial determinants shaping the co-occurrence patterns. Overall, these findings revealed the dynamics of prokaryotic taxa coexistence patterns in response to varying environmental conditions and further contributed to a broader understanding of microbial ecology in freshwater biogeochemical cycling.

Changes in the gut microbiome of patients with esophageal cancer: A systematic review and meta-analysis based on 16S gene sequencing technology.

BACKGROUND: Esophageal cancer (EC) possesses a high degree of malignancy and exhibits poor therapeutic outcomes and prognosis. However, its pathogenesis remains unclear. With the development of macrogene sequencing technology, changes in the intestinal flora have been found to be highly related to the development of EC, although discrepancies and controversies remain in this research area. MATERIALS AND METHODS: We comprehensively searched the PubMed, EMBASE, and Cochrane's Central Controlled Trials Register and the Scientific Network's database search projects based on systematically reviewed preferred reporting projects and meta-analyses. We used Engauge Digitizer for data extraction and Stata 15.1 for data analysis. In addition, we used the Newcastle-Ottawa Scale for grade grading and forest and funnel plots, sensitivity, and Egger and Beggar tests to evaluate the risk of bias. RESULTS: This study included 10 studies that assessed stool, tumor, and nontumor esophageal mucosa (gastroscopy and surgical resection) samples from 527 individuals, including 273 patients with EC and 254 healthy control group. We observed remarkable differences in microbial diversity in EC patients compared to healthy controls. The Chao1 index (46.01 vs. 42.67) was significantly increased in EC patients, whereas the Shannon index (14.90 vs. 19.05), ACE (39.24 vs. 58.47), and OTUs(28.93 vs. 70.10) were significantly lower. At the phylum level, the abundance of Bacteroidetes (37.89 vs. 32.77) increased significantly, whereas that of Firmicutes (37.63 vs. 38.72) decreased significantly; the abundance of Clostridium and Verruciformis increased, while that of Actinobacteria and Proteobacteria decreased to varying degrees. The abundance of Bacteroides (8.60 vs. 15.10) and Streptococcaceae (15.08 vs. 27.05) significantly reduced in EC. CONCLUSIONS: According to our meta-analysis, in patients with EC, the Chao1 index increased, whereas the Shannon and the OTUs decreased. At the phylum level, the abundance of Firmicutes decreased significantly, whereas that of Bacteroidetes and Proteobacteria increased significantly. At the genus/family level, the abundance of Bacteroidaceae, Prevotellaceae and Streptococcaceae decreased significantly, whereas that of Veillonellaceae increased. This meta-analysis identified changes in gut microbiota in patients with EC; however, its conclusions were inconsistent.

COE targets EphA2 to inhibit vasculogenic mimicry formation induced by hypoxia in hepatocellular carcinoma.

Background: Vasculogenic Mimicry (VM) can reduce the efficacy of anti-angiogenesis and promote distant metastasis in hepatocellular carcinoma (HCC). Our previous studies have found that Celastrus orbiculatus extract (COE) can inhibit the VM formation in HCC by reducing EphA2 expression. However the underlying mechanism related to EphA2 in VM formation is unclear. Purpose: This study aimed to confirm that EphA2 is one of the potential targets of COE, and to explore the effect of EphA2 in VM formation in hypoxia context in HCC. Methods: TCM Systems Pharmacology database and proteomics analysis were used to explore the key targets of COE in HCC treatment. CD31-PAS double staining and VE-CAD staining were used to indicate vasculogenic mimicry. The localization of EphA2 and VE-CAD was examined through fluorescent microscopy. CCK8 assay, cell invasion assay, and tube formation assay were used to indicate the formation of VM under hypoxic conditions. The regulatory relationship of EphA2 upstream and downstream molecules were evaluated through COIP and Western Blot. The nude mouse xenograft tumor models were used to observe the VM formation after knocking down or overexpressing EphA2. Results: EphA2 is identified to the target of COE, and the driving gene of HCC. In HCC surgical specimens, EphA2 expression is closely associated with the VM formation of HCC. COE-regulated EphA2 is involved in hypoxia-induced VM formation in HCC cells in vitro. EphA2 is regulated by HIF directly or indirectly by C-MYC. Overexpression of EphA2 can promote the VM formation of HCC in nude mice, while knocking down EphA2 can inhibit the VM formation. Conclusion: EphA2, as a target of COE, plays a crucial regulatory role in the formation of vasculogenic mimicry in HCC, involving upstream HIF/MYC transcriptional promotion and downstream PI3K/FAK/VE-CAD expression regulation.

Anatomy-specific Progression Classification in Chest Radiographs via Weakly Supervised Learning.

"Just Accepted" papers have undergone full peer review and have been accepted for publication in Radiology: Artificial Intelligence. This article will undergo copyediting, layout, and proof review before it is published in its final version. Please note that during production of the final copyedited article, errors may be discovered which could affect the content. Purpose To develop a machine learning approach for classifying disease progression in chest radiographs using weak labels automatically derived from radiology reports. Materials and Methods In this retrospective study, a twin neural network was developed to classify anatomy-specific disease progression into four categories: improved, unchanged, worsened, and new. A two-step weakly-supervised learning approach was employed, pretraining the model on 243,008 frontal chest radiographs from 63,877 MIMIC-CXR patients (mean age 51.7 years; female 34,813), and fine-tuning it on the subset with progression labels derived from consecutive studies. Model performance was evaluated for six pathologic observations on test datasets of unseen MIMIC-CXR patients. Area under the receiver operating characteristic (AUC) analysis was used to evaluate classification performance. The algorithm is also capable of generating bounding-box predictions to localize areas of new progression. Recall, precision, and mean average precision (mAP) were used to evaluate the new progression localization. One-tailed paired t tests were used to assess statistical significance. Results The model outperformed most baselines in progression classification, achieving macro AUC scores of 0.72 ± 0.004 for atelectasis, 0.75 ± 0.007 for consolidation, 0.76 ± 0.017 for edema, 0.81 ± 0.006 for effusion, 0.7 ± 0.032 for pneumonia, and 0.69 ± 0.01 for pneumothorax. For new observation localization, the model achieved mAP scores of 0.25 ± 0.03 for atelectasis, 0.34 ± 0.03 for consolidation, 0.33 ± 0.03 for edema, and 0.31 ± 0.03 for pneumothorax. Conclusion Disease progression classification models were developed on a large chest radiograph dataset, which can be used to monitor interval changes and detect new pathologies on chest radiographs. ©RSNA, 2024.

Accuracy evaluation of a universal dental implant guide for simulating implantation in posterior area on dental molds.

OBJECTIVES: This study aims to compare the accuracy of self-developed universal implant guide (SDG), 3D printed digital guide (DG), and free hand (FH) simulated implantation in the posterior tooth area of dental models. METHODS: Ten junior dentists were selected to place three implants in the 35, 37, and 46 tooth sites of the mandibular models (35, 36, 37, and 46 missing teeth) by using SDG, DG, and FH, and the process was repeated again to take the average value. Cone beam computed tomography (CBCT) was used to evaluate the global coronal deviation, global apical deviation, depth deviation, and angular deviation between the actual position and preoperative planned position. RESULTS: The coronal deviation and apical deviation of the three implant sites in the SDG group were not significantly different from those in the two other groups (P>0.05). The depth deviation and angular deviation in the SDG group were smaller than those in the DG group (P<0.05) and FH group (P<0.05), respectively. All deviations at site 37 in the SDG group were not different from those at site 35 (P>0.05), while the depth and angular deviation at site 37 in the DG group were higher than those at site 35 (P<0.05). CONCLUSIONS: The precision of the self-developed universal dental implant guide can meet the requirements of clinical posterior implantation.

PD-L2 mediates tobacco smoking-induced recruitment of regulatory T cells via the RGMB/NFκB/CCL20 cascade.

Programmed cell death ligand 2 (PD-L2), a ligand for the receptor programmed cell death 1 (PD-1), has an identity of 34% with its twin ligand PD-L1 and exhibits higher binding affinity with PD-1 than PD-L1. However, the role of PD-L2 in non-small cell lung cancer (NSCLC) progression, especially tobacco-induced cancer progression, has not been fully understood. Here, we found that PD-L2 promoted tumor growth in murine models with recruitment of regulatory T cells (Tregs). In patients with NSCLC, PD-L2 expression level in tumor samples was higher than in counterpart normal controls and was positively associated with patients' response to anti-PD-1 treatment. Mechanismly, PD-L2 bound its receptor Repulsive guidance molecule B (RGMB) on cancer cells and activated extracellular signal-regulated kinase (Erk) and nuclear factor κB (NFκB), leading to increased production of chemokine CCL20, which recruited Tregs and contributed to NSCLC progression. Consistently, knockdown of RGMB or NFκB p65 inhibited PD-L2-induced CCL20 production, and silencing of PD-L2 repressed Treg recruitment by NSCLC cells. Furthermore, cigarette smoke and carcinogen benzo(a)pyrene (BaP) upregulated PD-L2 in lung epithelial cells via aryl hydrocarbon receptor (AhR)-mediated transcription activation, whose deficiency markedly suppressed BaP-induced PD-L2 upregulation. These results suggest that PD-L2 mediates tobacco-induced recruitment of Tregs via the RGMB/NFκB/CCL20 cascade, and targeting this pathway might have therapeutic potentials in NSCLC.

The high-bone-mass phenotype of novel transgenic mice with LRP5 A241T mutation.

Gain-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) can cause high-bone-mass (HBM) phenotype, with 19 identified mutations so far. The A242T mutation in LRP5 has been found in 9 families, making it one of the most prevalent mutations. However, the correlation between the A242T mutation and HBM phenotype remains unverified in animal models. This study aimed to investigate the bone properties in a new transgenic mouse model carrying the LRP5 A241T missense mutation, equivalent to A242T in humans. Heterozygous Lrp5A241T mice were generated using CRISPR/Cas9 genome editing. Body weight increased with age from 4 to 16 weeks, higher in males than females, with no difference between Lrp5A241T mice and wild-type control. Micro-CT showed slightly longer femur and notably elevated trabecular bone mass of the femur and fifth lumbar spine with higher bone mineral density, bone volume fraction, and trabecular thickness in Lrp5A241T mice compared to wild-type mice. Additionally, increased cortical bone thickness and volume of the femur shaft and skull were observed in Lrp5A241T mice. Three-point bending tests of the tibia demonstrated enhanced bone strength properties in Lrp5A241T mice. Histomorphometry confirmed that the A241T mutation increased bone formation without affecting osteoblast number and reduced resorption activities in vivo. In vitro experiments indicated that the LRP5 A241T mutation enhanced osteogenic capacity of osteoblasts with upregulation of the Wnt signaling pathway, with no significant impact on the resorptive activity of osteoclasts. In summary, mice carrying the LRP5 A241T mutation displayed high bone mass and quality due to enhanced bone formation and reduced bone resorption in vivo, potentially mediated by the augmented osteogenic potential of osteoblasts. Continued investigation into the regulatory mechanisms of its bone metabolism and homeostasis may contribute to the advancement of novel therapeutic strategies for bone disorders.

IL-6 Inhibitor Tocilizumab Reduces Bone Resorption Around Implants with Bacterial Infection During Osseointegration: A Pilot Study in Rabbits.

PURPOSE: To evaluate the effect of interleukin-6 (IL-6) inhibitor (tocilizumab) on bacterial infection-associated bone resorption around implants during osseointegration in rabbits. MATERIALS AND METHODS: At total of 24 male, 9-monthold New Zealand white rabbits were included, and their two mandibular anterior teeth were extracted. Three months after extraction, 24 one-piece Dentium implants (Ø 2.5 mm, intraosseous length of 12 mm) were inserted in the anterior mandible, and the rabbits were divided into four groups (n = 6 per group). Different treatment methods were used in each group: blank control group (BC); only silk ligation (negative control [NC]); silk ligation and injection with minocycline hydrochloride ointment (positive control [PC]); and silk ligation and injection with tocilizumab at 8 mg/kg via the auricle vein (experimental [EP]). Eight weeks later, the animals were sacrificed, and samples were collected and then analyzed using microcomputed tomography (microCT) scanning, immunohistochemical analysis, and histologic analysis. RESULTS: From the microCT measurement, the ratio of the bone volume to the total volume (BV/TV) in the EP group was 67.00% ± 2.72%, which was higher than that in the other three groups (58.85% ± 2.43% in the BC group, 55.72% ± 2.48% in the PC group, and 36.52% ± 3.02% in the NC group). From immunohistochemical analysis, the expression of IL-6 was found to be higher in the NC group than in the BC, PC, and EP groups, but there was no statistical difference between these three groups. Furthermore, the RANKL (receptor activator of nuclear factor-κB ligand) expression was the lowest in the EP group, followed by the BC group, the PC group, and the NC group, which had the highest expression; there was no difference between the NC and PC groups. Upon histologic analysis, significant new bone was found on the implant surfaces in the EP group, sparse and less new bone could be seen in the BC and PC groups, and the most serious bone resorption occurred in the NC group. CONCLUSIONS: Tocilizumab, an inhibitor of IL-6, has a certain effect in preventing bone loss around implants caused by bacterial infection during the osseointegration period.

G272V and P301L Mutations Induce Isoform Specific Tau Mislocalization to Dendritic Spines and Synaptic Dysfunctions in Cellular Models of 3R and 4R Tau Frontotemporal Dementia.

Tau pathologies are detected in the brains of some of the most common neurodegenerative diseases including Alzheimer's disease (AD), Lewy body dementia (LBD), chronic traumatic encephalopathy (CTE), and frontotemporal dementia (FTD). Tau proteins are expressed in six isoforms with either three or four microtubule-binding repeats (3R tau or 4R tau) due to alternative RNA splicing. AD, LBD, and CTE brains contain pathological deposits of both 3R and 4R tau. FTD patients can exhibit either 4R tau pathologies in most cases or 3R tau pathologies less commonly in Pick's disease, which is a subfamily of FTD. Here, we report the isoform-specific roles of tau in FTD. The P301L mutation, linked to familial 4R tau FTD, induces mislocalization of 4R tau to dendritic spines in primary hippocampal cultures that were prepared from neonatal rat pups of both sexes. Contrastingly, the G272V mutation, linked to familial Pick's disease, induces phosphorylation-dependent mislocalization of 3R tau but not 4R tau proteins to dendritic spines. The overexpression of G272V 3R tau but not 4R tau proteins leads to the reduction of dendritic spine density and suppression of mEPSCs in 5-week-old primary rat hippocampal cultures. The decrease in mEPSC amplitude caused by G272V 3R tau is dynamin-dependent whereas that caused by P301L 4R tau is dynamin-independent, indicating that the two tau isoforms activate different signaling pathways responsible for excitatory synaptic dysfunction. Our 3R and 4R tau studies here will shed new light on diverse mechanisms underlying FTD, AD, LBD, and CTE.

Black rice diet alleviates colorectal cancer development through modulating tryptophan metabolism and activating AHR pathway.

Consumption of dietary fiber and anthocyanin has been linked to a lower incidence of colorectal cancer (CRC). This study scrutinizes the potential antitumorigenic attributes of a black rice diet (BRD), abundantly rich in dietary fiber and anthocyanin. Our results demonstrate notable antitumorigenic effects in mice on BRD, indicated by a reduction in both the size and number of intestinal tumors and a consequent extension in life span, compared to control diet-fed counterparts. Furthermore, fecal transplants from BRD-fed mice to germ-free mice led to a decrease in colonic cell proliferation, coupled with maintained integrity of the intestinal barrier. The BRD was associated with significant shifts in gut microbiota composition, specifically an augmentation in probiotic strains Bacteroides uniformis and Lactobacillus. Noteworthy changes in gut metabolites were also documented, including the upregulation of indole-3-lactic acid and indole. These metabolites have been identified to stimulate the intestinal aryl hydrocarbon receptor pathway, inhibiting CRC cell proliferation and colorectal tumorigenesis. In summary, these findings propose that a BRD may modulate the progression of intestinal tumors by fostering protective gut microbiota and metabolite profiles. The study accentuates the potential health advantages of whole-grain foods, emphasizing the potential utility of black rice in promoting health.

Metastatic clear cell sarcoma of the pancreas: From diagnosis to treatment.

This article presents a comprehensive case report on an uncommon instance of metastatic clear cell sarcoma (CCS) originating from the pancreas. The high mortality rate of pancreatic carcinoma underscores the importance of precise diagnosis and early detection. The authors report a novel case of CCS with pancreatic metastasis, detailing successful surgical intervention through distal pancreatectomy and splenectomy, resulting in favourable outcomes. This study highlights the standard role of surgery in treating advanced CCS and emphasizes preoperative imaging and thorough patient history assessment. This article also underscores the necessity for long-term surveillance due to the potential for recurrence or metastasis. Despite the favourable recovery postsurgery, the absence of subsequent follow-up evaluation prompts consideration of the need for extended monitoring. This article raises questions about the nature of the pancreatic lesion and suggests the possibility of a primary lesion. Further evidence is crucial to establish the correlation between the features related to the development of the patient's primary and metastatic tumours. In conclusion, this study offers valuable insights into metastatic CCS of the pancreas, highlighting the importance of regular postoperative follow-up for improved outcomes through early detection and intervention.

Effect of Sleeve Gastric Surgery on Body Weight and Hypothalamic-Pituitary Axis Hormone Levels in Patients with Polycystic Ovary Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder in women of reproductive age. It is difficult for patients with PCOS to achieve weight loss with conventional treatment. The aim of this study was to investigate weight loss and changes in hypothalamic-pituitary axis hormone levels in patients with PCOS combined with obesity after sleeve gastrectomy. METHODS: A retrospective analysis of 12 patients without PCOS and 24 patients with PCOS who underwent bariatric surgery at Beijing Luhe hospital from 2020 to 2022 was performed. The study assessed the changes in body weight and hormonal indexes of the hypothalamic-pituitary axis before and six months after the surgery. RESULTS: Patients with PCOS experienced greater weight loss compared to those without the condition. Following surgery, individuals with PCOS showed lower levels of postoperative testosterone, prolactin, and free testosterone indices compared to preoperative levels. Additionally, postoperative LH and FSH levels were higher than preoperative levels. Analysis of thyroid axis hormone levels revealed that FT3 and TSH levels were notably reduced in patients with PCOS postoperatively. Furthermore, growth hormone levels were found to be elevated in patients with PCOS following surgery. CONCLUSION: Bariatric surgery enhances hormone levels in the hypothalamic-pituitary axis in women with PCOS, leading to greater improvements in patients with PCOS compared to those with simple obesity.

Inhibition of the ATR-DNAPKcs-RB axis drives G1/S-phase transition and sensitizes triple-negative breast cancer (TNBC) to DNA holliday junctions.

Targeting the DNA damage response (DDR) is a promising strategy in oncotherapy, as most tumor cells are sensitive to excess damage due to their repair defects. Ataxia telangiectasia mutated and RAD3-related protein (ATR) is a damage response signal transduction sensor, and its therapeutic potential in tumor cells needs to be precisely investigated. Herein, we identified a new axis that could be targeted by ATR inhibitors to decrease the DNA-dependent protein kinase catalytic subunit (DNAPKcs), downregulate the expression of the retinoblastoma (RB), and drive G1/S-phase transition. Four-way DNA Holliday junctions (FJs) assembled in this process could trigger S-phase arrest and induce lethal chromosome damage in RB-positive triple-negative breast cancer (TNBC) cells. Furthermore, these unrepaired junctions also exerted toxic effects to RB-deficient TNBC cells when the homologous recombination repair (HRR) was inhibited. This study proposes a precise strategy for treating TNBC by targeting the DDR and extends our understanding of ATR and HJ in tumor treatment.