Cell softness regulates tumorigenicity and stemness of cancer cells.

Identifying and sorting highly tumorigenic and metastatic tumor cells from a heterogeneous cell population is a daunting challenge. Here, we show that microfluidic devices can be used to sort marker-based heterogeneous cancer stem cells (CSC) into mechanically stiff and soft subpopulations. The isolated soft tumor cells (< 400 Pa) but not the stiff ones (> 700 Pa) can form a tumor in immunocompetent mice with 100 cells per inoculation. Notably, only the soft, but not the stiff cells, isolated from CD133+ , ALDH+ , or side population CSCs, are able to form a tumor with only 100 cells in NOD-SCID or immunocompetent mice. The Wnt signaling protein BCL9L is upregulated in soft tumor cells and regulates their stemness and tumorigenicity. Clinically, BCL9L expression is correlated with a worse prognosis. Our findings suggest that the intrinsic softness is a unique marker of highly tumorigenic and metastatic tumor cells.

The mechanism of water oxidation using transition metal-based heterogeneous electrocatalysts.

The water oxidation reaction, a crucial process for solar energy conversion, has garnered significant research attention. Achieving efficient energy conversion requires the development of cost-effective and durable water oxidation catalysts. To design effective catalysts, it is essential to have a fundamental understanding of the reaction mechanisms. This review presents a comprehensive overview of recent advancements in the understanding of the mechanisms of water oxidation using transition metal-based heterogeneous electrocatalysts, including Mn, Fe, Co, Ni, and Cu-based catalysts. It highlights the catalytic mechanisms of different transition metals and emphasizes the importance of monitoring of key intermediates to explore the reaction pathway. In addition, advanced techniques for physical characterization of water oxidation intermediates are also introduced, for the purpose of providing information for establishing reliable methodologies in water oxidation research. The study of transition metal-based water oxidation electrocatalysts is instrumental in providing novel insights into understanding both natural and artificial energy conversion processes.

Facilely Direct Construction, White-Light Emission, and Color-Adjustable Luminescence of LaF3 :Pr3+ @SiO2 Yolk-Shell Nanospheres with Moisture Resistance.

Poor water stability and single luminous color are the major drawbacks of the most phosphors reported. Therefore, it is important to realize multicolor luminescence in a phosphor with single host and single activator as well as moisture resistance. LaF3 :Pr3+ @SiO2 yolk-shell nanospheres are facilely obtained by a designing new technology of a simple and cost-effective electrospray ionization combined with a dicrucible fluorating technique without using protective gas. In addition, tunable photoluminescence, especially white-light emission, is successfully obtained in LaF3 :Pr3+ @SiO2 yolk-shell nanospheres by adjusting Pr3+ ion concentrations, and the luminescence mechanism of Pr3+ ion is advanced. Compared with the counterpart LaF3 :Pr3+ nanospheres, the water stability of LaF3 :Pr3+ @SiO2 yolk-shell nanospheres is improved by 15% after immersion in water for 72 h, and the fluorescence intensity can be maintained at 86% of the initial intensity. Furthermore, by treating the yolk-shell nanospheres with hydrofluoric acid, it is not only demonstrated that the shell-layer is SiO2 but also core-LaF3 :Pr3+ nanospheres are obtained. Particularly, only fluorination procedure among the halogenation can produce such special yolk-shell nanospheres, the formation mechanism of yolk-shell nanospheres is proposed detailedly based on the sound experiments and a corresponding new technology is built. These findings broaden practical applications of LaF3 :Pr3+ @SiO2 yolk-shell nanospheres.

Mechanism of programmed cell death in the posterior silk gland of the silkworm, Bombyx mori, during pupation based on Ca2+ homeostasis.

The silkworm, Bombyx mori, is a complete metamorphosed economic insect, and the silk gland is a significant organ for silk protein synthesis and secretion. The silk gland completely degenerates during pupation, but the regulatory mechanism of programmed cell death (PCD) has not yet been understood. In the present study, we investigated the non-genetic pathway of 20E-induced PCD in the posterior silk gland (PSG) based on intracellular Ca2+ levels. Silk gland morphology and silk gland index indicated rapid degeneration of silk gland during metamorphosis from mature silkworm (MS) to pupal day 1 (P1), and Ca2+ levels within the PSG were found to peak during the pre-pupal day 1 (PP1) stage. Moreover, the results of autophagy and apoptosis levels within the PSG showed that autophagy was significantly increased in MS-PP1 periods, and significantly decreased in PP2 and P1 periods. Apoptosis was almost absent in MS-PP1 periods and significantly increased in PP2 and P1 periods. Additionally, western blotting results showed that autophagy preceded apoptosis, and the autophagy-promoting ATG5 was cleaved by calpain to the autophagy-inhibiting and apoptosis-promoting NtATG5 since PP1 period, while decreased autophagy was accompanied by increased apoptosis. Collectively, these findings suggest that Ca2+ is a key factor in the shift from autophagy to apoptosis.

Exposure to Progestin 17-OHPC Induces Gastrointestinal Dysfunction through Claudin 1 Suppression in Female Mice with Increased Anxiety-Like Behaviors.

INTRODUCTION: Progestin, commonly used in oral contraception and preventing preterm birth, elicits various off-target side effects on brain and gastrointestinal (GI) functions, yet the precise mechanisms remain elusive. This study aims to probe progestin's impact on GI function and anxiety-like behaviors in female mice. METHODS: Colon stem cells were utilized to explore the mechanism underlying progestin 17-hydroxyprogesterone caproate (17-OHPC)-mediated suppression of claudin-1 (CLDN1), crucial for epithelial integrity. Chromatin immunoprecipitation and luciferase assays identified potential progestin-response elements on the CLDN1 promoter, with subsequent assessment of oxidative stress and pro-inflammatory cytokine release. Manipulation of vitamin D receptor (VDR) or estrogen receptor ß (ERß) expression elucidated their roles in 17-OHPC-mediated effects. Intestine-specific VDR deficient mice were generated to evaluate 17-OHPC's impact on GI dysfunction and anxiety-like behaviors in female mice. Additionally, gene expression was analyzed in various brain regions, including the amygdala, hypothalamus, and hippocampus. RESULTS: Exposure to 17-OHPC suppressed CLDN1 expression via epigenetic modifications and VDR dissociation from the CLDN1 promoter. Furthermore, 17-OHPC intensified oxidative stress and proinflammatory cytokine release. VDR knockdown partly mimicked, while overexpression of either VDR or ERß partly restored 17-OHPC-mediated effects. Intestinal VDR deficiency partly mirrored 17-OHPC-induced GI dysfunction, with minimal impact on 17-OHPC-mediated anxiety-like behaviors. CONCLUSIONS: 17-OHPC suppresses CLDN1 expression through VDR, contributing to GI dysfunction in female mice, distinct from 17-OHPC-induced anxiety-like behaviors. This study reveals a new mechanism and potential negative impact of progestin exposure on the gastrointestinal tract, alongside inducing anxiety-like behaviors in female mice.

Differential expression of sNPF in male and female eyestalk leading to sex dimorphism of AMP expression in Procambarus clarkii intestine.

Antimicrobial peptide (AMP) is an important component of crustaceans' innate immune system. In this study, a short neuropeptide F (sNPF) gene (Pc-sNPF) and a Forkhead box O (FOXO) gene (PcFOXO) from Procambarus clarkii were identified. Analysis findings showed that the expression level of AMP genes differed between male and female P. clarkii. Furthermore, Pc-sNPF and PcFOXO were related to the sex dimorphism of AMP. Knockdown of Pc-sNPF in the eyestalk significantly upregulated the expression of PcFOXO and two anti-lipopolysaccharide factors (PcALF4 and PcALFL) in the intestine of P. clarkii. The expression of PcFOXO in the intestine of female P. clarkii was higher than in that of males. Results from RNA interference revealed that PcFOXO positively regulated the expression of PcALF4 and PcALFL in the intestine of male and female P. clarkii. In summary, our study showed that differences in Pc-sNPF expression in eyestalk of male and female P. clarkii leading to sex dimorphism of AMP expression in the intestine are mediated by the sNPF-FOXO-AMP signal pathway called the eyestalk-intestine axis.

KNTC1, regulated by HPV E7, inhibits cervical carcinogenesis partially through Smad2.

Cervical cancer is the second most common malignancy of the female reproductive tract worldwide. Although cervical cancer is caused by human papillomavirus (HPV) infection, its underlying pathogenesis requires further investigation. The present study investigated the role of kinetochore associated protein 1 (KNTC1) in cervical cancer and its association with the key virus oncoprotein, HPV E7. A series of bioinformatic analyses revealed that KNTC1 might be involved in the tumorigenesis of multiple human malignancies, including cervical cancer. Tissue microarray analysis showed that in vivo KNTC1 expression was higher in high-grade squamous intraepithelial lesions (HSILs) than in normal cervix and even higher in cervical cancer. In vitro silencing of KNTC1 increased the proliferation, invasion and migration of cervical cancer cell lines. Although not affecting apoptosis, KNTC1 silencing significantly promoted G1/S phase transition of the cell cycle. High-throughput analysis of mRNA expression showed that KNTC1 could regulate its downstream target protein Smad2 at the transcriptional level. Moreover, as the key oncoprotein of the virus, HPV E7 could inhibit the expression of KNTC1 protein, and decrease Smad2 protein expression with or without the aid of KNTC1. These results indicated that KNTC1 is a novel tumor suppressor that can impede the initiation and progression of cervical carcinoma, providing insight into the molecular mechanism by which HPV induces cervical cancer.

Hyperuricemia is associated with heart failure readmission in patients with heart failure and preserved ejection fraction-an observational study in Chinese.

BACKGROUND AND AIMS: This study aimed to explore the association between hyperuricemia and heart failure (HF) readmission in HF patients with preserved ejection fraction (HFpEF) because the impact of hyperuricemia on the prognosis of these patients has not been fully understood. METHODS AND RESULTS: This retrospective observational study included 538 hospitalized patients diagnosed with HFpEF. A total of 57.6 % of patients with HFpEF suffered from hyperuricemia (serum uric acid (SUA) was >7 mg/dL in men and >6 mg/dL in women). Compared to those without hyperuricemia, patients with hyperuricemia were more likely to be female (62.6 % vs. 53.9 %, p = 0.044) and older (78.0 ± 8.4 vs. 75.9 ± 9.0 years, p = 0.008). Our Cox analysis revealed that SUA level (hazard ratio (HR) = 1.158, 95 % confidence interval (CI): 1.087-1.234, p<0.001) and hyperuricemia (HR = 1.846, 95 % CI: 1.308-2.606, p<0.001) were associated with HF readmission in patients with HFpEF, respectively. Kaplan-Meier analysis showed that patients with hyperuricemia had a significantly worse prognosis (p<0.001). The receiver operating characteristic analysis revealed that the area under the ROC curve of SUA for predicting HF readmission was 0.6276 (95 % CI: 0.5763-0.6790) and a designated cut-off value of 7.53 mg/dL. CONCLUSIONS: Hyperuricemia is a common comorbidity among patients with HFpEF. Moreover, SUA level and hyperuricemia have been shown to be associated with HF readmission. Therefore, it is meaningful to monitor SUA levels in patients with HFpEF during the whole treatment period of HF. Whereas, whether intervention of hyperuricemia could benefit patients with HFpEF needs further studies.

Design, synthesis, in vitro and in vivo biological evaluation of pterostilbene derivatives for anti-inflammation therapy.

Pterostilbene (PST) is a naturally derived stilbene compound in grapes, blueberries, and other fruits. It is also a natural dietary compound with a wide range of biological activities such as antioxidant, anti-inflammatory, antitumor, and so on. Structural modifications based on the chemical scaffold of the pterostilbene skeleton are of great importance for drug discovery. In this study, pterostilbene skeletons were used to design novel anti-inflammatory compounds with high activity and low toxicity. A total of 30 new were found and synthesised, and their anti-inflammatory activity and safety were screened. Among them, compound E2 was the most active (against NO: IC50 = 0.7 µM) than celecoxib. Further studies showed that compound E2 exerted anti-inflammatory activity by blocking LPS-induced NF-κB/MAPK signalling pathway activation. In vivo experiments revealed that compound E2 had a good alleviating effect on acute colitis in mice. In conclusion, compound E2 may be a promising anti-inflammatory lead compound.

The Effect of Perioperative Comprehensive Nursing on Patients Undergoing Ovary Endometriosis Laparoscopic Surgery.

Objective: To assess the effectiveness of perioperative nursing interventions in improving outcomes and satisfaction for patients undergoing laparoscopic surgery for ovarian endometriosis. Methods: From July 2021 to September 2022, 80 patients with endometriosis underwent laparoscopic surgery at Shijiazhuang Fourth Hospital and were randomly assigned to the conventional (n=40) and experimental (n=40) groups. During the perioperative period, patients in the conventional group received standard nursing interventions, while patients in the experimental group received comprehensive nursing interventions. The two groups were compared in terms of postoperative clinical indicators, self-rated anxiety scale (SAS) and self-rated depression scale (SDS) scores, nursing compliance, complications, and nursing satisfaction. Results: comprehensive nursing resulted in better postoperative clinical indices (time to get out of bed, hospital stay) versus routine nursing (all P < .001). The comprehensive nursing led to significantly lower SAS and SDS scores versus routine nursing. The nursing compliance of the patients in the experimental group was significantly higher than that of the patients in the conventional group (P < .001). Comprehensive nursing was associated with a significantly lower incidence of complications versus routine nursing (P < .001). Comprehensive nursing contributed to significantly higher nursing satisfaction versus routine nursing (P < .001). Conclusion: Comprehensive perioperative nursing interventions for patients with ovarian endometriosis undergoing laparoscopic surgery considerably accelerate patient recovery and enhance nursing compliance, as well as minimize patient negative emotions and improve patient satisfaction with nursing.  The comprehensive approach addresses the specific needs of patients during the recovery period, minimizing postoperative complications, accelerating patient recovery, and improving overall quality of life. By integrating psychological support, tailored strategies for pain management, early mobilization, and prompt intervention for complications, this intervention sets a benchmark for holistic care in gynecological surgery.

Dynamic fecal microenvironment properties enable predictions and understanding of peripartum blood oxidative status and nonesterified fatty acids in dairy cows.

The transition period in dairy cows is a critical stage and peripartum oxidative status, negative energy balance (NEB), and inflammation are highly prevalent. Fecal microbial metabolism is closely associated with blood oxidative status and nonesterified fatty acids (NEFA) levels. Here, we investigated dynamic changes in total oxidative status markers and NEFA in blood, fecal microbiome, and metabolome of 30 dairy cows during transition (-21, -7, +7, +21 d relative to calving). Then the Bayesian network and 9 machine-learning algorithms were applied to dismantle their relationship. Our results show that the oxidative status indicator (OSI) of -21, -7, +7 d was higher than +21 d. The plasma concentration of NEFA peaked on +7 d. For fecal microenvironment, a decline in bacterial α diversity was observed at postpartum and in bacterial interactions at +7 d. Conversely, microbial metabolites involved in carbohydrate, lipid, and energy metabolism increased on +7 d. A correlation analysis revealed that 11 and 10 microbial metabolites contributed to OSI and NEFA variations, respectively (arc strength >0.5). The support vector machine (SVM) radial model showed the highest average predictive accuracy (100% and 88.9% in the test and external data sets) for OSI using 1 metabolite and 3 microbiota. The SVM radial model also showed the highest average diagnostic accuracy (100% and 91% in the test and external data sets) for NEFA with 2 metabolites and 3 microbiota. Our results reveal a relationship between variation in the fecal microenvironment and indicators of oxidative status, NEB, and inflammation, which provide a theoretical basis for the prevention and precise regulation of peripartum oxidative status and NEB.

Surface Superconductivity with High Transition Temperatures in Layered CanBn+1Cn+1 Films.

Proposed by Ginzberg nearly 60 years ago, surface superconductivity refers to the emergent phenomenon that the electrons on or near the surface of a material becomes superconducting despite its bulk is nonsuperconducting. Here, based on first-principles calculations within density functional theory, we predict that the superconducting transition temperature Tc at the surfaces of CanBn+1Cn+1 (n = 1, 2, 3, ...) films can be drastically enhanced to ∼90 K from 8 K for bulk CaBC. Our detailed analyses reveal that structural symmetry reduction at surfaces induces pronounced carrier self-doping into the surface B-C layer of the films and shifts the σ-bonding states toward the Fermi level; furthermore, the in-plane stretching modes of the surface layers experience significant softening. These two effects work collaboratively to strongly enhance the electron-phonon coupling, which in turn results in much higher Tc values than the McMillian limit. These findings point to new material platforms for realizing unusually high-Tc surface superconductivity.

[Related factors and equity of health status among floating population in China based on geographic information system analysis].

OBJECTIVE: To understand the health status, influencing factors and spatial distribution of the Chinese floating population and to evaluate the health equity of the floating population. METHODS: All the data were collected from the 2017 Migrant Population Dynamic Monitoring Survey in China, binary Logistic regression was used to analyze the factors that might affect the health of the floating population, and the concentration index method was used to evaluate the health equity of the floating population. Spatial autocorrelation analyses the spatial aggregation of health status and health equity. RESULTS: The unhealthy rate of the floating population in China was 2.71%. Age and gender show a statistically significant impact on self-rated health; that is, as age increases, the self-rated health of the migrant population gradually deteriorates, and women are more likely to think that they are unhealthy. Fairness analysis shows that the concentration index of the floating population is 0.021 7, the urban household registration floating population is 0.021 6, and the rural household registration floating population is 0.021 9. It is shown that the fairness of the health status of the floating population is biased towards the high-income class, and the rural household registration floating population' s health unfairness is greater than that of the urban household registration migration population. Moreover, Moran' s i=0.211 for self-rated health and Moran' s i=0.291 for the unhealthy rate indicate that self-rated health has a spatial aggregation trend. Moran' s i=0.136 showed the characteristics of spatial clustering, and the two-week prevalence fairness of the floating population was mainly in the northern and southeastern coastal areas. CONCLUSION: In general, the health status of the floating population in China is relatively good. The main influencing factors of health included gender and age. The central tendency of health inequity is reflected in the southeast coastal and northern regions, which are characterized by poverty. Attention to spatial aggregation is not only helpful to analyze the reasons of floating population, but also to study the health differences between different regions and health-related factors, to improve the overall health level of the whole population.

A BRD4-Targeting Photothermal Agent for Controlled Protein Degradation.

BRD4 protein plays a pivotal role in cell cycle regulation and differentiation. Disrupting the activity of BRD4 has emerged as a promising strategy for inhibiting the growth and proliferation of cancer cells. Herein, we introduced a BRD4-targeting photothermal agent for controlled protein degradation, aiming to enhance low-temperature photothermal therapy (PTT) for cancer treatment. By incorporating a BRD4 protein inhibitor into a cyanine dye scaffold, the photothermal agent specifically bond to the bromodomain of BRD4. Upon low power density laser irradiation, the agent induced protein degradation, directly destroying the BRD4 structure and inhibiting its transcriptional regulatory function. This strategy not only prolonged the retention time of the photothermal agent in cancer cells but also confined the targeted protein degradation process solely to the tumor tissue, minimizing side effects on normal tissues through the aid of exogenous signals. This work established a simple and feasible platform for future PTT agent design in clinical cancer treatment.

Cellular immunity in the era of modern multiple myeloma therapy.

Multiple myeloma (MM) is a relapsing clonal plasma cell malignancy and incurable thus far. With the increasing understanding of myeloma, highlighting the critical importance of the immune system in the pathogenesis of MM is essential. The immune changes in MM patients after treatment are associated with prognosis. In this review, we summarize currently available MM therapies and discuss how they affect cellular immunity. We find that the modern anti-MM treatments enhance antitumour immune responses. A deeper understanding of the therapeutic activity of individual drugs offers more effective treatment approaches that enhance the beneficial immunomodulatory effects. Furthermore, we show that the immune changes after treatment in MM patients can provide useful prognostic marker. Analysing cellular immune responses offers new perspectives for evaluating clinical data and making comprehensive predictions for applying novel therapies in MM patients.

Revised spectral optimization approach to remove surface-reflected radiance for the estimation of remote-sensing reflectance from the above-water method.

The effective sea-surface skylight reflectance (ρ) is an important parameter for removing the contribution of surface-reflected radiance when measuring water-leaving radiance (Lw) using the above-water approach (AWA). Radiative simulations and field measurements show that ρ varies spectrally. To improve the determination of Lw (and then remote sensing reflectance, Rrs) from the AWA, we further developed a wavelength-dependent model for ρ to remove surface-reflected radiance, which is applied with a spectral optimization approach for the determination of Rrs. Excellent agreement was achieved between the AWA-derived and skylight-blocked approach (SBA)-obtained Rrs (coefficient of determination > 0.92, mean absolute percentage deviation < ∼ 11% for Rrs > 0.0005 sr-1), even during high wave conditions. We found that the optimization approach with the new ρ model worked very well for a wide range of water types and observation geometries. For developing remote sensing algorithms and evaluating satellite products, it would be beneficial to apply this approach to current and historical above-water in situ measurements of Rrs to improve the quality of these data. In addition, this approach could also increase the number of useable spectra where previously rendered unusable when processed with a traditional scheme.

Histone deacetylase 9 exacerbates podocyte injury in hyperhomocysteinemia through epigenetic repression of Klotho.

Although hyperhomocysteinemia (hHcys) has been recognized as an important independent risk factor in the progression of end-stage renal disease and the development of cardiovascular complications related to end-stage renal disease, the mechanisms triggering pathogenic actions of hHcys are not fully understood. The present study was mainly designed to investigate the role of HDACs in renal injury induced by hHcys. Firstly, we identified the expression patterns of HDACs and found that, among zinc-dependent HDACs, HDAC9 was preferentially upregulated in the kidney from mice with hHcys. Deficiency or pharmacological inhibition of HDAC9 ameliorated renal injury in mice with hHcys. Moreover, podocyte-specific deletion of HDAC9 significantly attenuated podocyte injury and proteinuria. In vitro, gene silencing of HDAC9 attenuated podocyte injury by inhibiting apoptosis, reducing oxidative stress and maintaining the expressions of podocyte slit diaphragm proteins. Mechanically, we proved for the first time that HDAC9 reduced the acetylation level of H3K9 in the promoter of Klotho, then inhibited gene transcription of Klotho, finally aggravating podocyte injury in hHcys. In conclusion, our results indicated that targeting of HDAC9 might be an attractive therapeutic strategy for the treatment of renal injury induced by hHcys.

C-type lectin (CTL) and sialic acid-binding lectin (SABL) from Venerupis philippinarum: Function on PAMP binding and opsonic activities in immune responses.

Lectins are a superfamily of carbohydrate-recognition proteins that bind to specific carbohydrate structures and play significant roles in immune recognition and clearance of invaders. In the study, we investigated the potential mechanisms of PAMP binding and opsonic activities of a c-type lectin and a sialic acid-binding lectin from manila clam Venerupis philippinarum (designed as VpCTL and VpSABL). Both recombinant proteins (rVpCTL and rVpSABL) could bind LPS, PGN, glucan and zymosan in vitro. Coinciding with the PAMPs binding assay, a broad agglutination spectrum was displayed by rVpSABL including gram-positive bacteria Staphyloccocus aureus, gram-negative bacteria Escherichia coli, Vibrio parahaemolyticus, Vibrio harveyi, Pseudomonas putida, Proteus mirabilis and fungi Pichia pastoris, while no agglutinative activities on P. mirabilis and P. putida was observed in rVpCTL. Moreover, the phagocytosis and encapsulation ability of hemocytes could be significantly enhanced by rVpCTL and rVpSABL. More remarkable, VpCTL and VpSABL were highly detected in all the examined tissues, especially in gills and hepatopancreas. All the results showed that VpCTL and VpSABL could function as pattern recognition receptors (PRRs) with distinct recognition spectrum, perhaps involved in the innate immune responses of V. philippinarum.

Evidence from a meta-analysis for the prognostic and clinicopathological importance of DKC1 in malignancies.

Aim: We conducted a meta-analysis to evaluate the prognostic and clinicopathological relevance of DKC1 in various cancers. Methods: We searched Web of Science, Embase, PubMed, Wanfang and CNKI. Stata SE15.1 was used to calculate the hazard ratio and relative risk with 95% CIs to assess the possible correlations between DKC1 expression levels and overall and disease-free survival, as well as with clinicopathological parameters. Results: We included nine studies, with a total of 2574 patients. There was a meaningful link between elevated DKC1 and poorer disease-free (p < 0.001) and overall survival (p < 0.001). Also, it was linked to advanced tumor node metastasis stage (p = 0.005). Conclusion: High DKC1 expression was predictive of worse prognosis and poorer clinicopathological parameters.

What is this summary about? This brief summary reports the effects of high or low levels of a gene expression product called DKC1 on survival time and clinicopathological parameters in a small group of people with cancer. The DKC1 gene encodes a protein, DKC1, that is important for cancer cell proliferation. We systematically reviewed nine studies involving 2574 patients. What was the result? In this research, we revealed that people with cancer who had poor DKC1 expression had considerably longer survival without disease and better overall survival. In addition, the increased expression of DKC1 was linked to late-stage cancers. What do these results mean? The study has shown encouraging results, suggesting that DKC1 is a promising target for cancer therapy, as targeting it may hinder its ability to impair ribosome production and normal telomerase complex function to prolong patient life and prevent progression to a later disease stage. These studies demonstrate the need for more studies involving more people to definitively confirm how effective targeting DKC1 may be in treating cancer patients.

Discovery of pterostilbene analogs as novel NLRP3 inflammasome inhibitors for potential treatment of DSS-induced colitis in mice.

The pterostilbene skeleton is a promising chemical scaffold that exerts anti-inflammatory, anti-depressant, and anti-tumor effects. In this study, we aim to reduce in vivo and in vitro toxicity of compound 32 (preliminary work) and maintain its biological activity. A series of novel pterostilbene derivatives (D1-D43) were designed and synthesized, and their anti-inflammatory activities were screened. All compounds were screened to evaluate their inhibitory effect on LPS/Nigericin-induced IL-1ß production and pyroptosis. The structure-activity relationships was deduced, and finally 1-((E)-4-(2-ethoxyethoxy)styryl)-3,5-dimethoxy-2-((E)-2-nitrovinyl)benzene (D22) was found to be a low-toxic compound with most potent inhibitory efficacy (against IL-1ß: IC50 = 2.41 µM). Preliminary mechanism studies showed that compound D22 may affect the assembly of NLRP3 inflammasome by targeting NLRP3 protein, thereby inhibiting the activation of NLRP3 inflammasome. The in vivo anti-inflammatory activity indicated that compound D22 had significant therapeutic effects on DSS-induced mouse acute colitis models.