USP19 exerts a tumor-promoting role in diffuse large B cell lymphoma through stabilizing PARK7.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and is associated with a poor prognosis. Data from the Gene Expression Profiling Interactive Analysis (GEPIA) database revealed dysregulated expression of several ubiquitin-specific proteases (USPs) in DLBCL tissues (DLBCL vs. non-DLBCL = 47 vs. 337), including USP19 (log2fold change = 1.17, P < 0.05). USP19 is closely linked to tumorigenesis, but its role in DLBCL progression remains largely unknown. Here, we investigated the role of USP19 in DLBCL development. Genetic manipulation of USP19 using adenovirus-based vectors was performed in two DLBCL cell lines, SUDHL4 and DB cells. The results showed that USP19 knockdown suppressed the proliferation, anchorage-independent growth and xenograft tumor formation of DLBCL cells and arrested the cell cycle at the G1 stage. In parallel, DLBCL cells overexpressing USP19 acquired a more malignant phenotype. Next, to explore USP19 interactors, we performed co-immunoprecipitation/liquid chromatography-mass spectrometry and identified potential interacting proteins. Among them, Parkinson disease protein 7 (PARK7), a member of the peptidase C56 family known to be involved in carcinogenesis, was further validated to bind with and be stabilized by USP19. Additionally, we found that USP19 induced PARK7 deubiquitylation in both DLBCL cell lines, and PARK7 acted as a downstream effector of USP19 in regulating the growth of DLBCL cells. Collectively, USP19 exerts a tumor-promoting role in DLBCL through interacting with and stabilizing PARK7.

LMP1 enhances aerobic glycolysis in natural killer/T cell lymphoma.

Natural killer/T cell lymphoma (NKTCL) exhibits highly aggressive clinical behavior, and the outcomes for relapsed/refractory patients are still poor. Recently, the mechanism underlying the effect of Epstein-Barr virus (EBV) infection, which has not been fully defined in NKTCL, has attracted great attention. We explored how LMP1 promoted aerobic glycolysis via metabolic sequencing combined with mRNA sequencing and immunoprecipitation coupled to mass spectrometry. Experimental assays were used to determine the effects of LMP1 and its downstream pathway on the function and glucose metabolism of NKTCL cells. The correlations between LMP1 expression in patients and their clinical features, treatment response, and prognosis were analyzed. Results show that LMP1 enhances NKTCL cell proliferation in vitro and in vivo, inhibits apoptosis, and decreases gemcitabine sensitivity. In addition, LMP1 also enhances aerobic glycolysis in NKTCL cells, as indicated by increases in glucose uptake, lactate production, and extracellular acidification rate. Clinically, LMP1 expression is correlated with risk stratification, treatment response, and prognosis, and higher LMP1 expression indicates greater SUVmax for NKTCL patients. Mechanistically, LMP1 competitively binds to TRAF3 to promote cell proliferation and aerobic glycolysis by regulating the noncanonical NF-κB pathway. The application of an NF-κB pathway inhibitor or reactivation of the NF-κB pathway affects aerobic glycolysis and the biological function of NKTCL cells. In summary, this study is the first to describe and define in detail how LMP1 affects glucose metabolism in NKTCL and might provide a novel perspective for further treatment.

Comparison of Predictability in Vault Using NK Formula and KS Formula for the Implantable Collamer Lens Surgery.

Background: This study aims to investigate the agreement between the NK and KS formulas in predicting the vault after implantation of an EVO-implantable collamer lens (ICL). Methods: This retrospective study included 106 eyes of 57 patients who underwent ICL-V4c implantation. Preoperative vault prediction was conducted by utilizing the NK and KS formulas, with postoperative measurements by anterior segment optical coherence tomography (AS-OCT) at one month. The analysis focused on the consistency between predicted and achieved vaults, as well as the correlation between the achieved vault and various biometric parameters. Results: The mean achieved vault was 605.25 ± 212.72 µm, which was significantly smaller than the predicted vaults of 710.08 ± 195.08 and 673.80 ± 212.76 µm, using the NK and KS formulas, respectively (P < 0.05). The mean differences between the achieved vault and the predicted vault using the NK formula and KS formula were -104.82 µm (95% LoA: -600.38-391.19 µm) and -68.55 µm (95% LoA: -628.91-491.82 µm), respectively. Anterior chamber depth (ACD), vertical sulcus-to-sulcus (V-STS) diameter, and crystalline lens rise (CLR) were independent factors associated with the achieved vault (P < 0.05). The two formulas showed no statistically significant difference in absolute prediction error (APE). Conclusion: The NK formula exhibited superior consistency and low predictive error compared to the KS formula in the 12.6 mm ICL group. AS-OCT measurements overestimated the predicted ICL vault, especially in the 13.2 mm ICL size selection. Relying solely on the NK or KS formulas for predicting vaults before ICL surgery is not recommended.

Natural and synthetic 5-(3'-indolyl)oxazoles: Biological activity, chemical synthesis and advanced molecules.

5-(3'-Indolyl)oxazole moiety is a privileged heterocyclic scaffold, embedded in many biologically interesting natural products and potential therapeutic agents. Compounds containing this scaffold, whether from natural sources or synthesized, have demonstrated a wide array of biological activities. This has piqued the interest of synthetic chemists, leading to a large number of reported synthetic approaches to 5-(3'-indolyl)oxazole scaffold in recent years. In this review, we comprehensively overviewed the different biological activities and chemical synthetic methods for the 5-(3'-indolyl)oxazole scaffold reported in the literatures from 1963 to 2024. The focus of this study is to highlight the significance of 5-(3'-indolyl)oxazole derivatives as the lead compounds for the lead discovery of anticancer, pesticidal, antimicrobial, antiviral, antioxidant and anti-inflammatory agents, to summarize the synthetic methods for the 5-(3'-indolyl)oxazole scaffold. In addition, the reported mechanism of action of 5-(3'-indolyl)oxazoles and advanced molecules studied in animal models are also reviewed. Furthermore, this review offers perspectives on how 5-(3'-indolyl)oxazole scaffold as a privileged structure might be exploited in the future.

Vitamin D supplementation could enhance the effectiveness of glibenclamide in treating type 2 diabetes by improving the function of pancreatic ß-cells through the NF-κB pathway.

PURPOSE: The high morbidity and mortality associated with type 2 diabetes mellitus (T2DM) pose a significant global health challenge, necessitating the development of more efficient anti-diabetic drugs with fewer side effects. This study investigated the intervention of vitamin D3 combined with glibenclamide in rats with T2DM to elucidate its effects on pancreatic ß-cells through the NF-κB pathway. METHODS: Twenty-four healthy male Sprague-Dawley (SD) rats were randomly assigned to four groups: the control group (CG), the model group (MG), the glibenclamide group (GG), and the glibenclamide + vitamin D3 group (GDG). After inducing the T2DM model using high-fat and high-sugar diet and intraperitoneal injection of streptozotocin, the rats in the GG group were administered glibenclamide orally (0.6 mg/kg/day), while those in the GDG group received both glibenclamide (0.6 mg/kg/day) and vitamin D3 (500 IU/kg/day) in corn oil for a duration of 8 weeks. Biochemical indices were measured, and histopathological changes in pancreatic tissue and islet ß cells were observed using hematoxylin and eosin staining. The expression of pancreatic nuclear factor κB (NF-κB), islet ß-cells, and inflammatory cytokines were assessed using the TUNEL method and PCR. RESULTS: According to the data from this current study, the GDG group showed significant positive differences in plasma biochemical indices, as well as in the expression of ß cells, NF-κB p65, TNF-α, IL-1ß, INF-γ, and Fas, compared to the GG and CG groups (P < 0.05). CONCLUSION: The results suggest that vitamin D has beneficial effects on T2DM by improving the functions of islet ß cells through inhibition of the NF-κB signaling pathway. Therefore, it is suggested that vitamin D supplementation, when used alongside antidiabetic drugs, may more effectively prevent and treat T2DM.

Minimal residual disease detection in lymphoma: methods, procedures and clinical significance.

Lymphoma is a highly heterogeneous lymphohematopoietic tumor. As our understanding of the biological and pathological characteristics of lymphoma improves, we are identifying an increasing number of lymphoma subtypes. Genotyping has enhanced our ability to diagnose, treat, and monitor the prognosis of lymphoma. Despite significant improvements in treatment effectiveness, traditional methods for assessing disease response and monitoring prognosis are imperfect, and there is no significant improvement in overall remission rates for lymphoma patients. Minimal Residual Disease (MRD) is often indicative of refractory disease or early relapse. For lymphoma patients, personalized MRD monitoring techniques offer an efficient means to estimate disease remission levels, predict early relapse risk, and assess the effectiveness of new drug regimens. In this review, we delve into the MRD procedures in lymphoma, including sample selection and requirements, detection methods and their limitations and advantages, result interpretation. Besides, we also introduce the clinical applications of MRD detection in lymphoma.

Integrating ATAC-Seq and RNA-Seq Reveals the Signal Regulation Involved in the Artemia Embryonic Reactivation Process.

Embryonic diapause is a common evolutionary adaptation observed across a wide range of organisms. Artemia is one of the classic animal models for diapause research. The current studies of Artemia diapause mainly focus on the induction and maintenance of the embryonic diapause, with little research on the molecular regulatory mechanism of Artemia embryonic reactivation. The first 5 h after embryonic diapause breaking has been proved to be most important for embryonic reactivation in Artemia. In this work, two high-throughput sequencing methods, ATAC-seq and RNA-seq, were integrated to study the signal regulation process in embryonic reactivation of Artemia at 5 h after diapause breaking. Through the GO and KEGG enrichment analysis of the high-throughput datasets, it was showed that after 5 h of diapause breaking, the metabolism and regulation of Artemia cyst were quite active. Several signal transduction pathways were identified in the embryonic reactivation process, such as G-protein-coupled receptor (GPCR) signaling pathway, cell surface receptor signaling pathway, hormone-mediated signaling pathway, Wnt, Notch, mTOR signaling pathways, etc. It indicates that embryonic reactivation is a complex process regulated by multiple signaling pathways. With the further protein structure analysis and RT-qPCR verification, 11 GPCR genes were identified, in which 5 genes function in the embryonic reactivation stage and the other 6 genes contribute to the diapause stage. The results of this work reveal the signal transduction pathways and GPCRs involved in the embryonic reactivation process of Artemia cysts. These findings offer significant clues for in-depth research on the signal regulatory mechanisms of the embryonic reactivation process and valuable insights into the mechanism of animal embryonic diapause.

The output of cataract surgery performed by trained non-ophthalmologist physicians in rural areas: study of cataract outcomes and up-take of services report 7.

BACKGROUND: Cataract is the leading cause of blindness worldwide and surgery can restore vision in most patients. Some patients have little access to surgical services due to lack of cataract surgeons and the unaffordable costs. In 2005 we built a service model that trained rural non-ophthalmologist physicians to perform cataract surgeries in rural China. This study evaluates the long-term impacts of this model. METHODS: We conducted a retrospective cohort study to analyze patients' hand-written medical records and electronic outpatient record between January 2005 and December 2019 at two rural health clinics in Southern China. RESULTS: In total, 34,601 patients (49,942 eyes) underwent cataract surgery by non-ophthalmologist physicians from 2005 to 2019.Visual acuity was clearly documented in 38,251 eyes. Before surgery, the unaided distance visual acuity (UDVA) of 60.7% (23,205/38,251) eyes was less than 0.05 decimal. On the first day after surgery, the percentage of UDVA < 0.05 eyes was reduced to 6.0%, and 96.7% (36,980/38,251) of the eyes achieved a better UDVA compared to pre-operation. Surgical-related complications occurred in 218 eyes. The most common complication was posterior capsule rupture (114, 0.23%). 44.3% (15,341/34,601) of the patients chose to have a second eye cataract surgery (SECS) in the same clinic. At one of the outpatient clinics, 21,595 patients received basic eye care apart from cataract surgery between 2018 and 2020. CONCLUSIONS: Non-ophthalmologist physicians trained for cataract surgeries in rural clinics can improve cataract related visual acuity and basic eye care to the local population.

Clonal hematopoiesis of indeterminate potential contributes to accelerated chronic kidney disease progression.

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is a common inflammatory condition of aging that causes myriad end-organ damage. We have recently shown associations for CHIP with acute kidney injury and with kidney function decline in the general population, with stronger associations for CHIP driven by mutations in genes other than DNMT3A (non- DNMT3A CHIP). Longitudinal kidney function endpoints in individuals with pre-existing chronic kidney disease (CKD) and CHIP have been examined in two previous studies, which reported conflicting findings and were limited by small sample sizes. Methods: In this study, we examined the prospective associations between CHIP and CKD progression events in four cohorts of CKD patients (total N = 5,772). The primary outcome was a composite of 50% kidney function decline or kidney failure. The slope of eGFR decline was examined as a secondary outcome. Mendelian randomization techniques were then used to investigate potential causal effects of CHIP on eGFR decline. Finally, kidney function was assessed in adenine-fed CKD model mice having received a bone marrow transplant recapitulating Tet2 -CHIP compared to controls transplanted wild-type bone marrow. Results: Across all cohorts, the average age was 66.4 years, the average baseline eGFR was 42.6 ml/min/1.73m 2 , and 24% had CHIP. Upon meta-analysis, non- DNMT3A CHIP was associated with a 59% higher relative risk of incident CKD progression (HR 1.59, 95% CI: 1.02-2.47). This association was more pronounced among individuals with diabetes (HR 1.29, 95% CI: 1.03-1.62) and with baseline eGFR ≥ 30 ml/min/1.73m (HR 1.80, 95% CI: 1.11-2.90). Additionally, the annualized slope of eGFR decline was steeper among non- DNMT3A CHIP carriers, relative to non-carriers (ß -0.61 ± 0.31 ml/min/1.73m 2 , p = 0.04). Mendelian randomization analyses suggested a causal role for CHIP in eGFR decline among individuals with diabetes. In a dietary adenine mouse model of CKD, Tet2 -CHIP was associated with lower GFR as well as greater kidney inflammation, tubular injury, and tubulointerstitial fibrosis. Conclusion: Non- DNMT3A CHIP is a potentially targetable novel risk factor for CKD progression.

The diagnostic ability of peripapillary vessel density in primary open-angle glaucoma suspects.

OBJECTIVE: To assess the diagnostic ability of peripapillary vessel density (pVD) in primary open-angle glaucoma suspect (GS) patients. METHODS: Sixteen primary open-angle GS patients (22 eyes) and 20 normal controls (22 eyes) were included. In the GS group, OCTA measurements of pVD (superior, inferior, nasal, temporal, and global), OCT measurements of retinal nerve fiber layer (RNFL) thickness, disc area, rim area and ganglion cell complex (GCC) thickness were examined. In the control group, pVD measurements were performed. The vessel density between the two groups was compared. The correlation between OCTA and OCT parameters was evaluated. The receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of OCTA measurements. RESULTS: The global (P < 0.001), nasal (P = 0.003), and inferior (P = 0.002) quadrant pVD in GS group was considerably lower than the control group. The global pVD was positively correlated with the inferior RNFL thickness (r = 0.492, P = 0.023) and rim area (r = 0.483, P = 0.027). The inferior pVD was positively correlated with the inferior RNFL thickness (r = 0.648, P = 0.001), the nasal RNFL thickness (r = 0.441, P = 0.045), the rim area (r = 0.439, P = 0.046) and the GCC thickness (r = 0.472, P = 0.048). The global pVD had the best diagnostic value (AUC=0.825, sensitivity 86.36 %, specificity 72.73 %, cutoff value 45 %), followed by the inferior (AUC=0.749) and nasal (AUC=0.748) quadrant pVD. CONCLUSION: In primary open-angle GS patients, the global and inferior quadrant pVD was lower than that of normal people, and it was positively correlated with the inferior RNFL thickness and rim area. The diagnostic value of pVD for discriminating GS from normal people was excellent with high sensitivity and specificity.

Reconstruction of Eriocheir sinensis Protein-Protein Interaction Network Based on DGO-SVM Method.

Eriocheir sinensis is an economically important aquatic animal. Its regulatory mechanisms underlying many biological processes are still vague due to the lack of systematic analysis tools. The protein-protein interaction network (PIN) is an important tool for the systematic analysis of regulatory mechanisms. In this work, a novel machine learning method, DGO-SVM, was applied to predict the protein-protein interaction (PPI) in E. sinensis, and its PIN was reconstructed. With the domain, biological process, molecular functions and subcellular locations of proteins as the features, DGO-SVM showed excellent performance in Bombyx mori, humans and five aquatic crustaceans, with 92-96% accuracy. With DGO-SVM, the PIN of E. sinensis was reconstructed, containing 14,703 proteins and 7,243,597 interactions, in which 35,604 interactions were associated with 566 novel proteins mainly involved in the response to exogenous stimuli, cellular macromolecular metabolism and regulation. The DGO-SVM demonstrated that the biological process, molecular functions and subcellular locations of proteins are significant factors for the precise prediction of PPIs. We reconstructed the largest PIN for E. sinensis, which provides a systematic tool for the regulatory mechanism analysis. Furthermore, the novel-protein-related PPIs in the PIN may provide important clues for the mechanism analysis of the underlying specific physiological processes in E. sinensis.

Discovery of Novel Acethydrazide-Containing Flavonol Derivatives as Potential Antifungal Agents.

In this study, a series of novel hydrazide-containing flavonol derivatives was designed, synthesized, and evaluated for antifungal activity. In the in vitro antifungal assay, most of the target compounds exhibited potent antifungal activity against seven tested phytopathogenic fungi. In particular, compound C32 showed the best antifungal activity against Rhizoctonia solani (EC50 = 0.170 µg/mL), outperforming carbendazim (EC50 = 0.360 µg/mL) and boscalid (EC50 = 1.36 µg/mL). Compound C24 exhibited excellent antifungal activity against Valsa mali, Botrytis cinerea, and Alternaria alternata with EC50 values of 0.590, 0.870, and 1.71 µg/mL, respectively. The in vivo experiments revealed that compounds C32 and C24 were potential novel agricultural antifungals. 3D quantitative structure-activity relationship (3D-QSAR) models were used to analyze the structure-activity relationships of these compounds. The analysis results indicated that introducing appropriate electronegative groups at position 4 of a benzene ring could effectively improve the anti-R. solani activity. In the antifungal mechanism study, scanning electron microscopy and transmission electron microscopy analyses revealed that C32 disrupted the normal growth of hyphae by affecting the structural integrity of the cell membrane and cellular respiration. Furthermore, compound C32 exhibited potent succinate dehydrogenase (SDH) inhibitory activity (IC50 = 8.42 µM), surpassing that of the SDH fungicide boscalid (IC50 = 15.6 µM). The molecular dynamics simulations and docking experiments suggested that compound C32 can occupy the active site and form strong interactions with the key residues of SDH. Our findings have great potential for aiding future research on plant disease control in agriculture.

Development and evaluation of a large language model of ophthalmology in Chinese.

BACKGROUND: Large language models (LLMs), such as ChatGPT, have considerable implications for various medical applications. However, ChatGPT's training primarily draws from English-centric internet data and is not tailored explicitly to the medical domain. Thus, an ophthalmic LLM in Chinese is clinically essential for both healthcare providers and patients in mainland China. METHODS: We developed an LLM of ophthalmology (MOPH) using Chinese corpora and evaluated its performance in three clinical scenarios: ophthalmic board exams in Chinese, answering evidence-based medicine-oriented ophthalmic questions and diagnostic accuracy for clinical vignettes. Additionally, we compared MOPH's performance to that of human doctors. RESULTS: In the ophthalmic exam, MOPH's average score closely aligned with the mean score of trainees (64.7 (range 62-68) vs 66.2 (range 50-92), p=0.817), but achieving a score above 60 in all seven mock exams. In answering ophthalmic questions, MOPH demonstrated an adherence of 83.3% (25/30) of responses following Chinese guidelines (Likert scale 4-5). Only 6.7% (2/30, Likert scale 1-2) and 10% (3/30, Likert scale 3) of responses were rated as 'poor or very poor' or 'potentially misinterpretable inaccuracies' by reviewers. In diagnostic accuracy, although the rate of correct diagnosis by ophthalmologists was superior to that by MOPH (96.1% vs 81.1%, p>0.05), the difference was not statistically significant. CONCLUSION: This study demonstrated the promising performance of MOPH, a Chinese-specific ophthalmic LLM, in diverse clinical scenarios. MOPH has potential real-world applications in Chinese-language ophthalmology settings.

Comparison of immunochemotherapy and chemotherapy alone in conversion therapy for locally advanced unresectable esophageal squamous cell carcinoma.

Background: The clinical value of preoperative immunochemotherapy and simple chemotherapy induction regimen in the conversion therapy of locally advanced unresectable esophageal squamous cell carcinoma (ESCC) is still unclear. Method: Retrospective analysis was conducted on patients with unresectable cT4b stage ESCC who underwent conversion surgery in our hospital from January 2020 to December 2022. According to the preoperative induction treatment plan, they were divided into induction immunochemotherapy group (iICT group) and induction chemotherapy group (iCT group). The conversion surgery rate, R0 resection rate, radiological and pathological tumor responses, safety, and short-term survival outcomes were analyzed. Results: The results showed that a total of 199 patients with cT4b locally advanced unresectable ESCC who underwent preoperative induction therapy were included in this study. Among them, there were 64 cases (32.2%) in the iICT group, 135 cases (67.8%) in the iCT group. There was a statistically significant difference in objective response rate (73.5% vs 48.9%) and conversion surgery rate (81.3% vs 66.7%), between the iICT and iCT groups (P=0.001 and P=0.019). Among the two groups of patients who underwent surgery, there were statistically significant differences in R0 resection rate (94.2% vs 82.2%) and pathological complete remission rate (23.1% vs 6.7%) between the iICT and iCT groups (P=0.043 and P=0.004). And there was no statistically significant difference in the incidence of grade 3 and above between two groups (P=0.928). The 2-year EFS of the iICT group and iCT group were 76.4% and 42.4%, respectively, with statistically significant differences (P=0.006). Conclusions: Compared with simple chemotherapy, the combination of PD-1 inhibitors and chemotherapy can achieve better conversion surgery rate, tumor response and event-free survival in the conversion therapy of locally advanced unresectable ESCC.

Generative adversarial networks synthetic optical coherence tomography images as an education tool for image diagnosis of macular diseases: a randomized trial.

Purpose: This study aimed to evaluate the effectiveness of generative adversarial networks (GANs) in creating synthetic OCT images as an educational tool for teaching image diagnosis of macular diseases to medical students and ophthalmic residents. Methods: In this randomized trial, 20 fifth-year medical students and 20 ophthalmic residents were enrolled and randomly assigned (1:1 allocation) into Group real OCT and Group GANs OCT. All participants had a pretest to assess their educational background, followed by a 30-min smartphone-based education program using GANs or real OCT images for macular disease recognition training. Two additional tests were scheduled: one 5 min after the training to assess short-term performance, and another 1 week later to assess long-term performance. Scores and time consumption were recorded and compared. After all the tests, participants completed an anonymous subjective questionnaire. Results: Group GANs OCT scores increased from 80.0 (46.0 to 85.5) to 92.0 (81.0 to 95.5) 5 min after training (p < 0.001) and 92.30 ± 5.36 1 week after training (p < 0.001). Similarly, Group real OCT scores increased from 66.00 ± 19.52 to 92.90 ± 5.71 (p < 0.001), respectively. When compared between two groups, no statistically significant difference was found in test scores, score improvements, or time consumption. After training, medical students had a significantly higher score improvement than residents (p < 0.001). Conclusion: The education tool using synthetic OCT images had a similar educational ability compared to that using real OCT images, which improved the interpretation ability of ophthalmic residents and medical students in both short-term and long-term performances. The smartphone-based educational tool could be widely promoted for educational applications.Clinical trial registration: https://www.chictr.org.cn, Chinese Clinical Trial Registry [No. ChiCTR 2100053195].

Low potassium activation of proximal mTOR/AKT signaling is mediated by Kir4.2.

The renal epithelium is sensitive to changes in blood potassium (K+). We identify the basolateral K+ channel, Kir4.2, as a mediator of the proximal tubule response to K+ deficiency. Mice lacking Kir4.2 have a compensated baseline phenotype whereby they increase their distal transport burden to maintain homeostasis. Upon dietary K+ depletion, knockout animals decompensate as evidenced by increased urinary K+ excretion and development of a proximal renal tubular acidosis. Potassium wasting is not proximal in origin but is caused by higher ENaC activity and depends upon increased distal sodium delivery. Three-dimensional imaging reveals Kir4.2 knockouts fail to undergo proximal tubule expansion, while the distal convoluted tubule response is exaggerated. AKT signaling mediates the dietary K+ response, which is blunted in Kir4.2 knockouts. Lastly, we demonstrate in isolated tubules that AKT phosphorylation in response to low K+ depends upon mTORC2 activation by secondary changes in Cl- transport. Data support a proximal role for cell Cl- which, as it does along the distal nephron, responds to K+ changes to activate kinase signaling.

Palmitic acid reduces the methylation of the FOXO1 promoter to suppress the development of diffuse large B-cell lymphoma via modulating the miR-429/DNMT3A axis.

Diffuse large B-cell lymphoma (DLBCL) is characterized by significant treatment resistance. Palmitic acid (PA) has shown promising antitumor properties. This study aims to elucidate the molecular mechanisms by which PA influences DLBCL progression. We quantified the expression levels of microRNAs (miRNAs), Forkhead box protein O1 (FOXO1), and DNA methyltransferase 3A (DNMT3A) in both untreated and PA-treated DLBCL tumors and cell lines. Assessments were made of cell viability, apoptosis, and autophagy-related protein expression following PA administration. Interaction analyses among miR-429, DNMT3A, and FOXO1 were conducted using luciferase reporter assays and methylation-specific (MSP) Polymerase chain reaction (PCR). After transfecting the miR-429 inhibitor, negative control (NC) inhibitor, shRNA against DNMT3A (sh-DNMT3A), shRNA negative control (sh-NC), overexpression vector for DNMT3A (oe-DNMT3A), or overexpression negative control (oe-NC), we evaluated the effects of miR-429 and DNMT3A on cell viability, mortality, and autophagy-related protein expression in PA-treated DLBCL cell lines. The efficacy of PA was also tested in vivo using DLBCL tumor-bearing mouse models. MiR-429 and FOXO1 expression levels were downregulated, whereas DNMT3A was upregulated in DLBCL compared to the control group. PA treatment was associated with enhanced autophagy, mediated by the upregulation of miR-429 and downregulation of DNMT3A. The luciferase reporter assay and MSP confirmed that miR-429 directly inhibits DNMT3A, thereby reducing FOXO1 methylation. Subsequent experiments demonstrated that PA promotes autophagy and inhibits DLBCL progression by upregulating miR-429 and modulating the DNMT3A/FOXO1 axis. In vivo PA significantly reduced the growth of xenografted tumors through its regulatory impact on the miR-429/DNMT3A/FOXO1 axis. Palmitic acid may modulate autophagy and inhibit DLBCL progression by targeting the miR-429/DNMT3A/FOXO1 signaling pathway, suggesting a novel therapeutic target for DLBCL management.

A systematic literature review of 74 Chinese blastic plasmacytoid dendritic cell neoplasm patients.

Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological cancer. Due to its low incidence, researchers struggle to gather sufficient prospective data to inform clinical treatment. Objectives: We sought to summarize the clinical characteristics and current treatment methods of BPDCN and provide more specific guidance on treatment options. Design: A systematic literature review using data from 74 Chinese BPDCN patients. Date resources and methods: We retrospectively analyzed the clinical manifestations, treatment response, survival outcomes, and prognostic factors of six BPDCN patients treated at the First Affiliated Hospital of Zhengzhou University and 68 patients described in 28 articles published in the China Knowledge Network database since 2019. Results: In Chinese patients, the disease occurred with a male-to-female ratio of 2.52 and a median age of onset of 50 years in adults and 10 years in pediatric patients. Immunohistochemical analysis revealed distinctive immune phenotypes of BPDCN cells, characterized by high expression levels of CD4, CD56, CD123, and HLA-DR, while showing minimal to no expression of myeloperoxidase (MPO), CD20, and CD79a. There was no significant difference in the initial complete remission (CR) rate, relapse rate, and the overall survival (OS) time of patients receiving acute myeloid leukemia-like, acute lymphocytic leukemia-like, or non-Hodgkin's lymphoma-like chemotherapy regimens. Univariate analysis identified CD3 expression, male gender, and central nervous system infiltration as hazardous factors. In multivariate analysis, age proved to be an independent prognostic indicator, indicating better prognosis and longer OS time in younger patients. Notably, hematopoietic stem cell transplantation (HSCT) emerged as a significant factor in improving the survival outcomes for individuals diagnosed with BPDCN. However, further investigation is needed to explore the role of HSCT and the best timing for its implementation in pediatric BPDCN patients. Conclusion: Administering HSCT during the initial CR state following inductive chemotherapy might extend the OS and improve the prognosis of patients with BPDCN.

Systematic literature review of 74 BPDCN patients Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive neoplasm that derives from the precursors of plasmacytoid dendritic cell (pDC), accounting for 0.44% of hematological malignancy. Although CD123 targeted therapy has been implemented in the treatment of BPDCN, but a unique complication, capillary leak syndrome presents a therapeutic challenge, and retrospective analysis of conventional chemotherapy regimens is of irreplaceable importance for patients cannot tolerate CD123 targeted therapy. For the first time, we conduced retrospective analysis of large-scale clinical cases based on Chinese patients, and found that age and hematopoietic stem cell transplantation (HSCT) were two independent prognostic factors of BPDCN. In conclusion, younger patients had longer overall survival (OS) time and better prognosis. Combining HSCT in the initial complete remission state significantly prolonged the OS time and improved survival outcomes of BPDCN patients.

The impact of accelerating population aging on service industry development: Evidence from China.

The demographic structure is an important factor influencing the development of the services industry. As the country with the world's most serious aging problem, China's service industry structure is likely to undergo profound changes in response to the rapid demographic transition. Therefore, this paper examines the effect of population aging on the development of the service industry in the context of China's accelerating population aging. The study found that: (1) Population aging has a significant "inverted U" effect on the development of the services industry. (2) The impact of population aging on the development of the service industry has obvious regional and industry heterogeneity. The study of regional heterogeneity found that population aging in economically developed regions has a more obvious effect on the development of the service industry than in economically less developed regions. Industry heterogeneity studies found that population aging has an obvious promotional effect on the development of medical and other rigid demand industries, while the effect on other non-rigid demand industries is not significant. (3) The threshold effect test found that when the degree of population aging exceeds the threshold, the stimulating effect of population aging on the development of the services industry is no longer significant. The research in this paper provides useful insights into the likely response to changes in the industrial structure of the services industry, and offers some implications for countries with similar demographic profiles to China.