Streptomyces albidocamelliae sp. nov., an endophytic actinomycete isolated from the leaves of Camellia oleifera.

A novel actinobacterium strain, HUAS 14-6T, was isolated from the healthy leaves of Camellia oleifera collected from Changde City, Hunan Province, China. Strain HUAS 14-6T produced tight spiral spore chains consisting of oval or spherical spores with a smooth surface. 16S rRNA gene sequence analysis revealed that strain HUAS 14-6T belonged to the genus Streptomyces and shared highest similarity to Streptomyces bungoensis DSM 41781T (99.72%). Phylogenetic analysis based on 16S rRNA gene sequences indicated strain HUAS 14-6T was in a clade with S. bungoensis DSM 41781T. However, the ANIm and dDDH between strain HUAS 14-6T and S. bungoensis DSM 41781T were 88.16% and 31.2%, respectively, far less than the species-level thresholds. Phylogenetic trees based on the five housekeeping genes (atpD, gyrB, recA, rpoB and trpB) showed that strain HUAS 14-6T formed a separate branch, indicating that this strain could belong to a potential new species. Pairwise MLSA distances between strain HUAS 14-6T and all type strains exhibiting 16S rRNA gene sequence similarities of ≥98.7% to it were much higher than the maximum range of 0.014 recommended for delineating a new Streptomyces species. Based on polyphasic taxonomic study, HUAS 14-6T represents a novel species within the genus Streptomyces for which the name Streptomyces albidocamelliae sp. nov. is proposed. The type strain is HUAS 14-6T (=MCCC 1K08365T=JCM 35920T).

Drainage of ascites in cirrhosis.

For cirrhotic refractory ascites, diuretics combined with albumin and vasoactive drugs are the first-line choice for ascites management. However, their therapeutic effects are limited, and most refractory ascites do not respond to medication treatment, necessitating consideration of drainage or surgical interventions. Consequently, numerous drainage methods for cirrhotic ascites have emerged, including large-volume paracentesis, transjugular intrahepatic portosystemic shunt, peritoneovenous shunt, automated low-flow ascites pump, cell-free and concentrated ascites reinfusion therapy, and peritoneal catheter drainage. This review introduces the advantages and disadvantages of these methods in different aspects, as well as indications and contraindications for this disease.

Pulmonary delivery of forsythin-phospholipid complexes improves the lung anti-inflammatory efficacy in mice by enhancing dissolution and lung tissue affinity.

Forsythin, currently in phase II clinical trials in China for the treatment of the common cold and influenza, faces challenges in achieving adequate lung drug exposure due to its limited dissolution and permeability, thereby restricting its therapeutic efficacy. The objective of this work was to formulate a forsythin-phospholipid complex (FPC) to enhance its dissolution properties and lung affinity with a particular view to improving pulmonary drug exposure and anti-inflammatory response. The results revealed that forsythin reacted with dipalmitoyl-phosphatidylcholine to form a stable, nanosized FPC suspension. This formulation significantly improved the in vitro drug's dissolution, cellular uptake, and lung affinity compared to its uncomplexed form. Intratracheal administration of FPC in a mouse model of acute lung injury induced by lipopolysaccharide (LPS) resulted in a substantial increase in drug exposure to lung tissues (39.6-fold) and immune cells in the epithelial lining fluid (198-fold) compared to intraperitoneal injection. In addition, FPC instillation exhibited superior local anti-inflammatory effects, leading to improved survival rates among mice with LPS-induced acute respiratory distress syndrome, outperforming both instilled forsythin and injected FPC. Overall, this work demonstrated the potential of phospholipid complexes as a viable option for developing inhalation products for drugs with limited solubility and permeability properties.

Talarmalnoids A-F: Fusicoccane diterpenoids from an arthropod-derived endophytic fungus Talaromyces malicola.

The metabolites from the endophytic fungus Talaromyces malicola hosted in the gastrointestinal tract of the arthropods Armadillidium vulgare were investigated, and six undescribed fusicoccane diterpenoids, talarmalnoids A-F (1-6), along with three known analogs were isolated. Talarmalnoid C (3) was an unprecedented fusicoccane diterpenoid with two sugar units, i.e., 6-O-methyl-α-d-glucose and α-d-glucose. Talarmalnoids D and E (4 and 5) were fusicoccane-type diterpenoids with unusual seven-membered rings attached at the C-3' and C-4' positions. Their structures and absolute configurations were identified by NMR, HRESIMS analyses, X-ray single crystal diffraction, GC-MS, ECD analyses, 13C NMR calculations, and DP4+ probability analyses. Bioassay results showed that talarmalnoid B (2) exhibited significant inhibitory activities against the LPS-inducted production of NO in RAW 264.7 cells, with IC50 value of 0.83 µM.

Neural encoding for spatial release from informational masking and its correlation with behavioral metrics.

The central auditory system encompasses two primary functions: identification and localization. Spatial release from masking (SRM) highlights speech recognition in competing noise and improves the listening experience when a spatial cue is introduced between noise and target speech. This assessment focuses on the integrity of auditory function and holds clinical significance. However, infants or pre-lingual subjects sometimes provide less reliable results. This study investigates the value of cortical auditory evoked potentials (CAEPs) onset and acoustic change complex (ACC) as an objective measurement of SRM. Thirty normal-hearing young adults (11 males) were recruited. We found the spatial separation of signals and noise (±90° symmetrically) resulted in a signal-to-noise ratio (SNR) improvement of 9.00 ± 1.71 dB behaviorally. It significantly enhanced cortical processing at all SNR levels, shortened CAEP latencies, and increased amplitudes, resulting in a greater number of measurable peaks for ACC. SRM showed mild to moderate correlations with the differences between two conditions in CAEP measures. The regression model combining N1'-P2' amplitude at 5 dB SNR (R2 = 0.26), P1 amplitude at 0 dB SNR (R2 = 0.14), and P1 latency at -5 dB SNR (R2 = 0.15), explained 45.3% of the variance in SRM. Our study demonstrates that introducing spatial cues can improve speech perception and enhance central auditory processing in normal-hearing young adults. CAEPs may contribute to predictions about SRM and hold potential for practical application.NEW & NOTEWORTHY The neural encoding of spatial release from masking (SRM) can be observed in normal-hearing young adults. Spatial separation between target and masker improves speech perception in noise and enhances central auditory processing. The behavioral results showed mild-to-moderate correlations with electrophysiological measures, with acoustic change complex (ACC) amplitude being a better indicator than onset components. Cortical auditory evoked potentials (CAEPs) may contribute to predictions about spatial release from masking, especially when behavioral tests are less reliable.

The Side-Release Method Measures the High-Pressure Sound Velocity of Iron Using Line-Spatially Resolved DISAR.

The study of high-pressure sound velocity is an important part of shock wave physics, and the study of ultra-high pressure sound velocity of iron is of great significance to many research fields such as geophysics, solid state physics, and crystallography. At present, the measurement of sound velocity is usually carried out by the catch-up sparse wave method and windowed VISAR technology, which is complex in structure and not highly adaptable. In particular, for the ultra-high pressure sonic velocity measurement of metals, it is limited by the loading platform and window materials and cannot realize the high temperature and high-pressure environment of the earth's inner core. In this paper, the sound velocity measurement of iron under high temperature and high-pressure environment (78 GPa) is realized based on the two-stage light gas cannon experimental platform. The side-side sparse wave method was used to establish a coupling model of high-spatially resolved optical group and fiber bundle. A multiplexed all-fiber laser interferometry velocity measurement system (DISAR) was built, and the spatial resolution was better than 20 µm. In this paper, we will provide a feasible route for a method for measuring the high spatiotemporal resolution velocity.

Research on failure mechanism of landslide with retaining-wall-like locked segment and instability prediction by inverse velocity method.

The locked segment is critical for determining the stability of locked segment-type landslides. Research indicates that the volume expansion point marks the transition from the secondary creep stage to the tertiary creep stage in a landslide's evolution, and also separates the stable crack growth stage from the unstable crack growth stage in the locked segment. Identifying the volume expansion point is essential for early warning and predicting locked segment-type landslides. A series of instruments (resistance strain gauges, acoustic emission system, piezoelectric acceleration sensors, etc.) were used to conduct physical model tests of the landslide with retaining-wall-like locked segment under external load on the landslide's trailing edge. The evolution process of this landslide was analyzed through changes in slope shape and stress response characteristics. The experimental results reveal the failure mechanism of the landslide with retaining-wall-like locked segment: the upper part of the landslide thrusts and slides, the middle part squeezes and uplifts, the retaining-wall-like locked segment produces a locking effect, and compression-shear fracture of the retaining-wall-like locked segment leads to landslide failure. Based on the deformation and acoustic emission characteristics of the locked segment, a method for identifying the volume expansion point was established. This point was used as the onset of acceleration point in the inverse velocity method to predict the failure time of the locked segment-type landslides, incorporating the three-stage creep model and Fukumoto's theory.

[Secondary metabolites of endophytic fungus Talaromyces malicola hosted in Armadillidium vulgare].

The secondary metabolites of the endophytic fungus Talaromyces malicola hosted in the arthropod Armadillidium vulgare were separated by silica gel column chromatography, gel column chromatography, and semi-preparative high-performance liquid chromatography. Eleven compounds(1-11) were obtained from the ethyl acetate fraction of the fermentation broth of T. malicola, and their structures were identified by NMR, HR-ESI-MS, UV, IR, and ECD. The 11 compounds were talarosesquiterpene A(1),(3ß,5α,6α,15α,22E)-5,6-epoxyergosta-8(14),22-diene-3,7,15-triol(2), vermistatin(3), hydroxyvermistatin(4), bercheminol A(5), penicillide(6), lunatinin(7), penipurdin A(8), emodin(9), BE-25327(10), and(-)-regiolone(11). Compound 1 was a new diaporol-type sesquiterpene. Compounds 2, 4-5, and 7-11 were isolated from Talaromyces for the first time.

1D Anionic Covalent Organic Frameworks With Directed Migration of Alkali Metal Ions for High Ionic Conductivity.

Rational construction of high-performance ionic conductors is a critical challenge in the field of energy storage. In this study, a series of 1D anionic titanium-based covalent organic frameworks (COFs) containing abundant alkali metal ion migration sites, namely, COF-M-R (M = Li, Na, K; R = H, Me, Et), is constructed. The integration of negative TiO6 2- sites on 1D anionic COFs allows alkali metal cations to migrate directly through the channels. Meanwhile, the π-π stacking of 1D chain-to-chain allows the distribution of ion-migration sites in 2D planes. In view of this, multidimensional ionic transport in COFs is realized to achieve high ionic conductivity. COF-M-Rs exhibit an increased ionic conductivity as the counterions change from Li+ to Na+ to K+. Notably, COF-Na-Et has an impressive ionic conductivity as high as 0.81 × 10-3 S cm-1. The different decorated groups (H, Me, and Et) on the skeleton influence the dissociation of the cation from the polyanion. This study offers deep insights into the design of COF-based solid-state electrolytes to achieve high ionic conductivity by increasing the ionic transport dimensions.

TRIB3 knockdown increases the sensitivity of clear cell renal cell carcinoma to sunitinib by inducing ferroptosis.

Sunitinib resistance presents a significant challenge in the treatment of clear cell renal cell carcinoma (ccRCC). The role of TRIB3, a newly identified oncogene, in tumor drug resistance has been widely studied. However, the mechanism by which TRIB3 contributes to sunitinib resistance in ccRCC has not been previously explored. This study aimed to investigate the mechanism through which TRIB3 regulates ferroptosis to increase the susceptibility of ccRCC to sunitinib treatment. Bioinformatics analysis and experimental validation revealed that TRIB3 is significantly upregulated in ccRCC tissues and is associated with poor prognosis. Knockdown of TRIB3 using siRNA transfection inhibited the proliferation and migration of ccRCC cells and induced ferroptosis. Following sunitinib treatment, TRIB3 knockdown increased cell sensitivity to sunitinib, enhanced the suppressive impact of sunitinib, and augmented sunitinib-induced ferroptosis. This study demonstrated that TRIB3 knockdown induces ferroptosis by targeting the SLC7A11/GPX4 pathway and enhances therapeutic efficacy of sunitinib for ccRCC, providing new insights and potential strategies to overcome the challenge of sunitinib resistance in ccRCC.

Photodynamic Therapy Using RGD-Functionalized Quantum Dots Elicit a Potent Immune Response in a Syngeneic Mouse Model of Pancreatic Cancer.

Purpose: Photodynamic therapy (PDT) induces anti-tumor immune responses by triggering immunogenic cell death in tumor cells. Previously, we demonstrated that novel QDs-RGD nanoparticles exhibited high efficiency as photosensitizers in the treatment of pancreatic cancer. However, the underlying mechanism of the anti-tumor immune effects induced by the photosensitizer remains unknown. This study assessed the anticancer immune effect of QDs-RGD, as well as the conventional photosensitizer chlorine derivative, YLG-1, for comparison, against pancreatic cancer in support of superior therapeutic efficacy. Methods: The pancreatic cancer cell line, Panc02, was used for in vitro studies. C57BL/6 mice bearing pancreatic cancer cell-derived xenografts were generated for in vivo studies to assess the anti-tumor effects of QDs-RGD-PDT and YLG-1-PDT. The immunostimulatory ability of both photosensitizers was examined by measuring the expression of damage-associated molecular patterns (DAMP), such as calreticulin (CRT), assessing dendritic cell (DC) maturation, and analyzing cytokine expression. The specific immunity of QDs-RGD and YLG-1-PDT on distant tumor were determined by combining PDT with anti-CTLA-4 antibody. Results: QDs-RGD-PDT and YLG-1-PDT significantly inhibited pancreatic cancer cell growth in a dose- and time-dependent manner. While both photosensitizers significantly promoted CRT release, DC maturation, and interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α) expression, QDs-RGD exerted a stronger immunostimulatory effect than YLG-1. Combination treatment with QDs-RGD and CTLA-4 blockade was able to significantly inhibit the growth of distant tumors. Conclusion: QDs-RGD is a novel and effective PDT strategy for treating pancreatic tumors by inducing anti-tumor immune responses.

[Correlation of environment temperature with the incidence of testicular torsion].

Objective： To explore the influence of environment temperature on the incidence of testicular torsion. METHODS: We collected the clinical data on 172 cases of testicular torsion diagnosed in the Second Hospital of Hebei Medical University from December 2013 to December 2020. According to the local environment temperature on the day of onset, we divided the patients into groups A (below 0℃), B (0－10℃), C (10－20℃) and D (above 20℃), and compared the incidence rates of testicular torsion among the four groups, followed by correlation analysis. RESULTS: The incidence rate of testicular torsion was 12.8% (n = 22) in group A, 35.5% (n = 61) in B, 34.9% (n = 60) in C and 16.9% (n = 29) in D, the highest at 0－10℃ in group B, with statistically significant difference among the four groups (χ2 = 29.07, P <0.001). Spearman correlation analysis indicated that the incidence of testicular torsion was negatively correlated with the environment temperature (r = －0.261, P <0.01), with no statistically significant difference among different seasons (χ2 = 5.349, P >0.05), but higher in autumn and winter than in the other two seasons. CONCLUSION: The incidence of testicular torsion is negatively correlated with the environment temperature, elevated when the temperature decreases, but has no statistically significant difference among different seasons, though relatively higher in autumn and winter.

Senescent endothelial cells: a potential target for diabetic retinopathy.

Diabetic retinopathy (DR) is a diabetic complication that results in visual impairment and relevant retinal diseases. Current therapeutic strategies on DR primarily focus on antiangiogenic therapies, which particularly target vascular endothelial growth factor and its related signaling transduction. However, these therapies still have limitations due to the intricate pathogenesis of DR. Emerging studies have shown that premature senescence of endothelial cells (ECs) in a hyperglycemic environment is involved in the disease process of DR and plays multiple roles at different stages. Moreover, these surprising discoveries have driven the development of senotherapeutics and strategies targeting senescent endothelial cells (SECs), which present challenging but promising prospects in DR treatment. In this review, we focus on the inducers and mechanisms of EC senescence in the pathogenesis of DR and summarize the current research advances in the development of senotherapeutics and strategies that target SECs for DR treatment. Herein, we highlight the role played by key factors at different stages of EC senescence, which will be critical for facilitating the development of future innovative treatment strategies that target the different stages of senescence in DR.

AUY922 improves sensitivity to sunitinib in clear cell renal cell carcinoma based on network pharmacology and in vitro experiments.

Clear Cell Renal Cell Carcinoma (ccRCC), the most prevalent form of renal cell carcinoma (RCC), poses a significant threat to human health due to its rising morbidity and mortality rates. Sunitinib, a pivotal targeted drug for the treatment of ccRCC, presents a significant challenge due to the high susceptibility of ccRCC to resistance. HSP90 inhibitor AUY922 has demonstrated anti-tumor activity in a range of cancer types. However, its efficacy in combination with sunitinib for ccRCC treatment has not been evaluated. In this study, we employed bioinformatics, network pharmacology, and in vitro assays to verify that AUY922 inhibits cell viability, proliferation, and migration of ccRCC cell lines 786-O and ACHN, with IC50s of 91.86 µM for 786-O and 115.5 µM for ACHN. The effect of AUY922 enhancing the inhibitory effect of sunitinib on ccRCC was further confirmed. The CCK-8 assay demonstrated that the IC50 of sunitinib was reduced from 15.10 µM to 11.91 µM for 786-O and from 17.65 µM to 13.66 µM for ACHN, after the combined application of AUY922. The EdU assay and wound healing assay indicated that AUY922 augmented the inhibitory impact of sunitinib on the proliferation and migration of ccRCC cells. Western blot and RT-PCR analyses demonstrated that AUY922 increased the sensitivity of ccRCC cells to sunitinib by targeting the HIF-1α/VEGFA/VEGFR pathway. Our study represents the first investigation into the role and mechanism of AUY922 in enhancing the sensitivity of ccRCC to sunitinib. In conclusion, the findings indicate the potential for AUY922 to enhance the therapeutic efficacy of sunitinib and overcome sunitinib resistance in ccRCC.

Peptidomic analysis reveals novel peptide PDLC promotes cell proliferation in hepatocellular carcinoma via Ras/Raf/MEK/ERK pathway.

Hepatocellular carcinoma (HCC) still presents poor prognosis with low overall survival rates and limited therapeutic options available. Recently, attention has been drawn to peptidomic analysis, an emerging field of proteomics for the exploration of new potential peptide drugs for the treatment of various diseases. However, research on the potential function of HCC peptides is lacking. Here, we analyzed the peptide spectrum in HCC tissues using peptidomic techniques and explored the potentially beneficial peptides involved in HCC. Changes in peptide profiles in HCC were examined using liquid chromatography-mass spectrometry (LC-MS/MS). Analyze the physicochemical properties and function of differently expressed peptides using bioinformatics. The effect of candidate functional peptides on HCC cell growth and migration was evaluated using the CCK-8, colony formation, and transwell assays. Transcriptome sequencing analysis and western blot were employed to delve into the mode of action of potential peptide on HCC. Peptidomic analysis of HCC tissue yielded a total of 8683 peptides, of which 452 exhibited up-regulation and 362 showed down-regulation. The peptides that were differentially expressed, according to bioinformatic analysis, were closely linked to carbon metabolism and the mitochondrial inner membrane. The peptide functional validation identified a novel peptide, PDLC (peptide derived from liver cancer), which was found to dramatically boost HCC cell proliferation through the Ras/Raf/MEK/ERK signaling cascade. Our research defined the peptide's properties and pattern of expression in HCC and identified a novel peptide, PDLC, with a function in encouraging HCC progression, offering an entirely new potential therapeutic target the disease.

Vasorin (VASN) overexpression promotes pulmonary metastasis and resistance to adjuvant chemotherapy in patients with locally advanced rectal cancer.

BACKGROUND: LARC patients commonly receive adjuvant therapy, however, hidden micrometastases still limit the improvement of OS. This study aims to investigate the impact of VASN in rectal cancer with pulmonary metastasis and understand the underlying molecular mechanisms to guide adjuvant chemotherapy selection. METHODS: Sequencing data from rectal cancer patients with pulmonary metastasis from Sun Yat-sen University Cancer Center (SYSUCC) and publicly available data were meticulously analyzed. The functional role of VASN in pulmonary metastasis was validated in vivo and in vitro. Coimmunoprecipitation (co-IP), immunofluorescence, and rescue experiments were conducted to unravel potential molecular mechanisms of VASN. Moreover, VASN expression levels in tumor samples were examined and analyzed for their correlations with pulmonary metastasis status, tumor stage, adjuvant chemotherapy benefit, and survival outcome. RESULTS: Our study revealed a significant association between high VASN expression and pulmonary metastasis in LARC patients. Experiments in vitro and in vivo demonstrated that VASN could promote the cell proliferation, metastasis, and drug resistance of colorectal cancer. Mechanistically, VASN interacts with the NOTCH1 protein, leading to concurrent activation of the NOTCH and MAPK pathways. Clinically, pulmonary metastasis and advanced tumor stage were observed in 90% of VASN-positive patients and 53.5% of VASN-high patients, respectively, and VASN-high patients had a lower five-year survival rate than VASN-low patients (26.7% vs. 83.7%). Moreover, the Cox analysis and OS analysis indicated that VASN was an independent prognostic factor for OS (HR = 7.4, P value < 0.001) and a predictor of adjuvant therapy efficacy in rectal cancer. CONCLUSIONS: Our study highlights the role of VASN in decreasing drug sensitivity and activating the NOTCH and MAPK pathways, which leads to tumorigenesis and pulmonary metastasis. Both experimental and clinical data support that rectal cancer patients with VASN overexpression detected in biopsies have a higher risk of pulmonary metastasis and adjuvant chemotherapy resistance.

Regulating the Double-Way Traffic of Cations and Anions in Ambipolar Polymer Cathodes for High-Performing Aluminum Dual-Ion Batteries.

The strong Coulombic interactions between Al3+ and traditional inorganic crystalline cathodes present a significant obstacle in developing high-performance rechargeable aluminum batteries (RABs) that hold promise for safe and sustainable stationary energy storage. While accommodating chloroaluminate ions (AlCl4 -, AlCl2+, etc.) in redox-active organic compounds offers a promising solution for RABs, the issues of dissolution and low ionic/electronic conductivities plague the development of organic cathodes. Herein, electron donors are synthetically connected with acceptors to create crosslinked, bipolar-conjugated polymer cathodes. These cathodes exhibit overlapped redox potential ranges for both donors and acceptors in highly concentrated AlCl3-based ionic liquid electrolytes. This approach strategically enables on-site doping of the polymer backbones during redox reactions involving both donor and acceptor units, thereby enhancing the electron/ion transfer kinetics within the resultant polymer cathodes. Based on the optimal donor/acceptor combination, the bipolar polymer cathodes can deliver a high specific capacity of 205 mAh g-1 by leveraging the co-storage of AlCl4 - and AlCl2+. The electrodes exhibit excellent rate performance, a stable cycle life of 60 000 cycles, and function efficiently at high mass loadings, i.e., 100 mg cm-2, and at low temperatures, i.e., -30 °C. The findings exemplify the exploration of high-performing conjugated polymer cathodes for RABs through rational structural design.

[Isolation and identification of malonyl ginsenoside-Ra_1 and malonyl ginsenoside-Ra_2 from fresh roots of Panax ginseng].

The aim of this paper is to study the malonyl ginsenosides in the fresh roots of Panax ginseng. D101 macroporous adsorption resin, ODS, and preparative HPLC were employed to separate the chemical components from the 70% ethanol extract of the fresh roots of P. ginseng, and the structures of the separated compounds were identified based on the data of high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Two malonyl ginsenosides were isolated from the fresh roots of P. ginseng and identified as 3-O-\[6-O-malonyl-ß-D-glucopyranosyl-(1→2)-ß-D-glucopyranosyl\]-20-O-\[ ß-D-xylopyranosyl-(1→4)-α-L-arabinopyranosyl-(1→6)-ß-D-glucopyranosyl\]-dammar-24-ene-3ß,12ß,20S-triol(1) and 3-O-\[6-O-malonyl-ß-D-glucopyranosyl-(1→2)-ß-D-glucopyranosyl\]-20-O-\[ ß-D-xylopyranosyl-(1→2)-α-L-arabinofuranosyl-(1→6)-ß-D-glucopyranosyl\]-dammar-24-ene-3ß,12ß,20S-triol(2), respectively. Compounds 1 and 2 are new compounds isolated from fresh roots of P. ginseng for the first time and named as malonyl ginsenoside-Ra_1 and malonyl ginsenoside-Ra_2, respectively.

REEP4 as Potential Biomarker Associated with Predictive Prognosis and Immune Response in Kidney Clear Cell Carcinoma.

Kidney clear cell carcinoma (KIRC) commonly presents with metastases upon diagnosis, highlighting the critical need to identify more precise biomarkers for early detection, intervention, and personalized treatment. Although The REEP family has been investigated in cancer development, the specific relationship between REEP4 and cancer remains unclear. In our study, we employed bioinformatics analysis and conducted fundamental experiments to evaluate the potential of REEP4 as a biomarker for predicting the prognosis and therapeutic efficacy of KIRC. Comparing KIRC tumor tissues to normal tissues, we observed a significant upregulation in REEP4 expression, with higher levels of REEP4 correlating positively with tumor malignancy. Further COX regression analysis, as well as single and multifactorial analyses, confirmed that high REEP4 expression indicated lower survival rates in KIRC. Gene function analysis also identified associations between REEP4 and critical pathways such as the cell cycle, along with its involvement in protein binding. Furthermore, our investigation of the immune response suggests that a favorable immunotherapeutic response is linked to a reduction in REEP4 expression. Subsequently, we conducted in vitro experiments to confirm the overexpression of REEP4 in KIRC tumor tissues and renal cancer cells. In summary, our study revealed a close association between REEP4 expression and KIRC, emphasizing its correlation with prognosis and the immune response. These findings suggest that REEP4 is a potential biomarker for KIRC.

The Global Incident Gastrointestinal Cancers Attributable to Suboptimal Diets From 1990 to 2018.

BACKGROUND & AIMS: The contribution of suboptimal diets to gastrointestinal (GI) cancer incidence globally remains unquantified, and we aimed to evaluate it. METHODS: Comprehensive meta-analyses and rigorous evidence-grading assessment identified the associations between suboptimal diets and 6 GI cancers and their subtypes. A comparative risk assessment model was used to estimate the proportional attributable burden and attributable rate of GI cancers to suboptimal diets by using the corroborative association estimates. In addition, correlation assessments with the Sociodemographic Index were carried out. RESULTS: In 2018, 21.5% (95% uncertainty interval, 19.1%-24.5%) of incident GI cancer cases globally were attributable to suboptimal diets, maintaining a relatively stable proportion since 1990 (22.4%; 19.7%-25.6%), whereas the absolute diet-attributable cases doubled from 580,862 (510,658-664,076) in 1990 to 1,039,877 (923,482-1,187,244) in 2018. Excessive processed meat consumption (5.9%; 4.2%-7.9%), insufficient fruit intake (4.8%; 3.8%-5.9%), and insufficient whole grain intake (3.6%; 2.8%-5.1%) were the most significant dietary risk factors in 2018, a shift from 1990 when the third major concern was insufficient nonstarchy vegetable intake. In addition, Central and Eastern Europe and Central Asia experienced the highest attributable burden across regions in both 1990 (31.6%; 27.0%-37.4%) and 2018 (31.6%; 27.3%-36.5%), and a positive correlation (P < .001) between the Sociodemographic Index and the attributable GI cancer incidence was observed. CONCLUSIONS: Although the proportional attributable GI incidence remains relatively stable, the doubling of absolute cases from 1990 to 2018, along with the discrepancies among urbanicity and countries/regions, informs dietary priorities and more targeted preventive measures.