Juvenile hormone-induced microRNA miR-iab-8 regulates lipid homeostasis and metamorphosis in Drosophila melanogaster.

Metamorphosis plays an important role in the evolutionary success of insects. Accumulating evidence indicated that microRNAs (miRNAs) are involved in the regulation of processes associated with insect metamorphosis. However, the miRNAs coordinated with juvenile hormone (JH)-regulated metamorphosis remain poorly reported. In the present study, using high-throughput miRNA sequencing combined with Drosophila genetic approaches, we demonstrated that miR-iab-8, which primarily targets homeotic genes to modulate haltere-wing transformation and sterility was up-regulated by JH and involved in JH-mediated metamorphosis. Overexpression of miR-iab-8 in the fat body resulted in delayed development and failure of larval-pupal transition. Furthermore, metabolomic analysis results revealed that overexpression of miR-iab-8 caused severe energy metabolism defects especially the lipid metabolism, resulting in significantly reduced triacylglycerol (TG) content and glycerophospholipids but enhanced accumulation of phosphatidylcholine (PC) and phosphatidylethanolamine (PE). In line with this, Nile red staining demonstrated that during the third larval development, the TG content in the miR-iab-8 overexpression larvae was continuously decreased, which is opposite to the control. Additionally, the transcription levels of genes committed to TG synthesis and breakdown were found to be significantly increased and the expression of genes responsible for glycerophospholipids metabolism were also altered. Overall, we proposed that JH induced miR-iab-8 expression to perturb the lipid metabolism homeostasis especially the TG storage in the fat body, which in turn affected larval growth and metamorphosis.

Strain Effect on Dielectricity of Elastic Thermoplastic Polyurethanes.

Dielectric elastomers, such as thermoplastic polyurethanes (TPUs), are widely used as the dielectric layer, encapsulation layer, and substrate of flexible and stretchable devices. To construct capacitors and actuators that work stably upon deformation, it has become urgent to investigate the evolution of dielectricity under stress and strain. However, the lack of effective methods for estimating the dielectric constant of elastomers under strain poses a big challenge. This study reports a device for the in situ measurement of the dielectric constant of TPU under strain. It is found that upon stretching TPU to a strain of 400%, its dielectric constant decreases from 8.02 ± 0.01 to 2.88 ± 0.25 (at 1 MHz). In addition, combined Fourier-transform infrared spectroscopy, the X-ray scattering technique, and atomic force microscopy were utilized to characterize the evolution of the microstructure under strain. The investigation under tensile strain reveals a decreased density and average size of polarized hard domains, along with a tendency of the molecular chains to align in parallel with the tensile stress. The evolution of the microstructures results in a reduction in the measured dielectric constant in TPU.

Juvenile hormone signal transducer hairy inhibits Krüppel homolog1 expression.

Hairy and Krüppel homolog 1 (Kr-h1) are transcriptional repressors that act synergistically to mediate the gene-repressive action of juvenile hormone (JH). However, whether a regulatory relationship exists between Hairy and Kr-h1 remains unclear. In this study, an inhibitory effect of Hairy on Kr-h1 expression was found. Genetic studies in Drosophila have shown that the simultaneous overexpression of Hairy and Kr-h1 can rescue the defective phenotypes caused by the overexpression of a single factor. Reduced expression of Kr-h1 was observed in Hairy-overexpressing flies and cells, whereas the expression levels of Hairy were unaffected in cells with ectopic expression of Kr-h1. The inhibitory effect of Hairy on Kr-h1 expression was found to occur at the transcriptional level, as Hairy bound directly to the B-box within the Kr-h1 promoter via the bHLH motif and recruited the corepressors C-terminal binding protein (CtBP) and Groucho (Gro) through the PLSLV and WRPW motifs, respectively. Our findings revealed a regulatory relationship between two JH response factors, which advances our understanding of the molecular mechanism of JH signaling.

Advances in Flexible Magnetosensitive Materials and Devices for Wearable Electronics.

Emerging fields, such as wearable electronics, digital healthcare, the Internet of Things, and humanoid robots, highlight the need for flexible devices capable of recording signals on curved surfaces and soft objects. In particular, flexible magnetosensitive devices garner significant attention owing to their ability to combine the advantages of flexible electronics and magnetoelectronic devices, such as reshaping capability, conformability, contactless sensing, and navigation capability. Several key challenges must be addressed to develop well-functional flexible magnetic devices. These include determining how to make magnetic materials flexible and even elastic, understanding how the physical properties of magnetic films change under external strain and stress, and designing and constructing flexible magnetosensitive devices. In recent years, significant progress is made in addressing these challenges. This study aims to provide a timely and comprehensive overview of the most recent developments in flexible magnetosensitive devices. This includes discussions on the fabrications and mechanical regulations of flexible magnetic materials, the principles and performances of flexible magnetic sensors, and their applications for wearable electronics. In addition, future development trends and challenges in this field are discussed.

Classical swine fever virus non-structural protein 4A recruits dihydroorotate dehydrogenase to facilitate viral replication.

Mitochondria are energy producers in cells, which can affect viral replication by regulating the host innate immune signaling pathways, and the changes in their biological functions are inextricably linked the viral life cycle. In this study, we screened a library of 382 mitochondria-targeted compounds and identified the antiviral inhibitors of dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme in the de novo synthesis pathway of pyrimidine ribonucleotides, against classical swine fever virus (CSFV). Our data showed that the inhibitors interfered with viral RNA synthesis in a dose-dependent manner, with half-maximal effective concentrations (EC50) ranging from 0.975 to 26.635 nM. Remarkably, DHODH inhibitors obstructed CSFV replication by enhancing the innate immune response including the TBK1-IRF3-STAT1 and NF-κB signaling pathways. Furthermore, the data from a series of compound addition and supplementation trials indicated that DHODH inhibitors also inhibited CSFV replication by blocking the de novo pyrimidine synthesis. Remarkably, DHODH knockdown demonstrated that it was essential for CSFV replication. Mechanistically, confocal microscopy and immunoprecipitation assays showed that the non-structural protein 4A (NS4A) recruited and interacted with DHODH in the perinuclear. Notably, NS4A enhanced the DHODH activity and promoted the generation of UMP for efficient viral replication. Structurally, the amino acids 65-229 of DHODH and the amino acids 25-40 of NS4A were pivotal for this interaction. Taken together, our findings highlight the critical role of DHODH in the CSFV life cycle and offer a potential antiviral target for the development of novel therapeutics against CSF. IMPORTANCE: Classical swine fever remains one of the most economically important viral diseases of domestic pigs and wild boar worldwide. dihydroorotate dehydrogenase (DHODH) inhibitors have been shown to suppress the replication of several viruses in vitro and in vivo, but the effects on Pestivirus remain unknown. In this study, three specific DHODH inhibitors, including DHODH-IN-16, BAY-2402234, and Brequinar were found to strongly suppress classical swine fever virus (CSFV) replication. These inhibitors target the host DHODH, depleting the pyrimidine nucleotide pool to exert their antiviral effects. Intriguingly, we observed that the non-structural protein 4A of CSFV induced DHODH to accumulate around the nucleus in conjunction with mitochondria. Moreover, NS4A exhibited a strong interaction with DHODH, enhancing its activity to promote efficient CSFV replication. In conclusion, our findings enhance the understanding of the pyrimidine synthesis in CSFV infection and expand the novel functions of CSFV NS4A in viral replication, providing a reference for further exploration of antiviral targets against CSFV.

Revolutionizing T3-4N0-2M0 gastric cancer staging with an innovative pathologic N classification system.

BACKGROUND: The current pathologic N (pN) classification exhibits limitations in the prognostic stratification of patients with pT3-4N0-2M0 gastric cancer (GC). Therefore, this study aimed to develop and validate a new lymph nodal staging method based on the number of examined lymph nodes (ELNs) and lymph node ratio (LNR). METHODS: Data from 7883 patients with pT3-4N0-2M0 GC were collected from the Surveillance, Epidemiology, and End Results (SEER) database and Zhejiang Cancer Provincial Hospital. Optimal cutoff values for ELNs and LNR were determined using X-tile software. Kaplan-Meier methods, Log-rank tests, and Cox regression analyses were employed in this study. Patients were categorized into 3 new pN stages: new pN0 (pN0 with ELNs of >16), new pN1 (pN0 with ELNs of ≤16 or pN1-2 with LNR of ≤0.15), and new pN2 (pN1-2 with LNR of >0.15). The prognostic predictive power of both current and new pN staging was evaluated using the Akaike information criterion (AIC), Bayesian information criterion, concordance index (C-index), and receiver operating characteristic curve. RESULTS: The new pN classification exhibited excellent performance in Kaplan-Meier survival analysis. After adjusting for confounding factors, the new pN staging emerged as an independent prognostic indicator in patients with GC. In the SEER cohort, the new pN staging demonstrated enhanced prognostic prediction accuracy over the American Joint Committee on Cancer pN staging (AIC: 75578.85 vs 75755.06; C-index: 0.642 vs 0.630; P < .001). Similar findings were validated in the Chinese cohort. CONCLUSION: This study developed and validated an improved pN classification for patients with pT3-4N0-2M0 GC. Surgeons should consider ELNs and LNR when assessing postoperative prognosis in patients with GC.

Antioxidant aromatic compounds from Amomum villosum and target prediction of active ingredients.

The dried fruit of Amomum villosum is an important spice and medicinal plant that has received great attention in recent years due to its high content of bioactive components and its potential for food additives and drug development. However, the stems and leaves of A. villosum are usually disposed of as waste. Based on the study of the fruits of A. villosum, we also systematically studied its stems and leaves. Fourteen aromatic compounds (1-14) were isolated and identified from A. villosum, including five new compounds (1-5) and nine known compounds (6-14). Among them, compounds 2-5, 8-10, 12-13 were obtained from the fruits of A. villosum, and compounds 1, 6-7,11, 14 were isolated from the stems and leaves of A. villosum. Based on chemical evidence and spectral data analysis (UV, ECD, Optical rotation data, 1D and 2D-NMR, and HR-ESI-MS), the structures of new compounds were elucidated. Furthermore, all compounds were tested for their effects on the survival rate of BV-2 cells in the presence of hydrogen peroxide. Among them, compound 5 showed antioxidant effects. Through network pharmacology screening and the cell thermal shift assay (CETSA), the Phosphoglycerate Mutase 5 (PGAM5) protein was identified as the antioxidant target of compound 5. Molecular docking results showed that compound 5 maintains binding to PGAM5 by forming hydrogen bond interactions with Lys93 and Agr214. In summary, A. villosum had potential medicinal and food values due to the diverse bioactive components.

A retrospective study: exploring the optimal patient population for adjuvant chemotherapy after D2 gastrectomy.

BACKGROUND: Adjuvant chemotherapy (CT) constitutes the primary approach for treating resectable advanced gastric cancer (GC). However, the effectiveness of postoperative CT can differ across various patient groups. This retrospective study aimed to examine how variances in clinical and pathologic factors affect postoperative CT. METHODS: This study enrolled 2060 patients with GC who underwent curative gastrectomy at Zhejiang Cancer Hospital between January 2008 and December 2017, with 1277 receiving postoperative CT. This study used Kaplan-Meier to determine the effect of clinical and pathology factors on CT benefits. In addition, univariate and multivariate Cox regression analyses were used to identify independent prognosis risk factors. RESULTS: Both univariate and multivariate analyses demonstrated that the absence of postoperative CT is an independent factor associated with a poor prognosis in patients with GC. The Kaplan-Meier univariate analysis revealed that specific subgroups, including males, those with a normal body mass index (BMI), the elderly, individuals with gastric adenocarcinoma, cases of nerve invasion by the tumor, vascular invasion by the tumor, tumor size ≥ 5 cm, and Tumor, Node, Metastasis (TNM) stage III, exhibited improved treatment outcomes with the administration of postoperative CT. The creation of nomograms using Cox regression and the rms package holds significant clinical relevance. CONCLUSION: Postoperative CT is advantageous for prolonging the survival of advanced patients undergoing D2 gastrectomy, particularly in male patients, the elderly, individuals with a normal BMI score, those diagnosed with gastric adenocarcinoma, cases, in which the tumor invades nerves or blood vessels, patients with a tumor size of ≥5 cm, and those with a TNM stage of III, as it results in improved treatment outcomes within these subgroups.

Prognostic significance of serum tumor markers in various pathologic subtypes of gastric cancer.

PURPOSE: This study aimed to assess the utility of 6 serum tumor markers in prognosis between gastric adenocarcinoma and gastric signet ring cell carcinoma (SRCC). METHODS: A cohort of 3131 cases of gastric adenocarcinoma and 275 cases of gastric SRCC was assembled. The serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125, alpha fetoprotein (AFP), carbohydrate antigen 242 (CA242), and carbohydrate antigen 724 (CA724) were measured in all cases. The study analyzed the association between the levels of these 6 tumor markers and the prognosis of gastric adenocarcinoma and SRCC. RESULTS: The study revealed that gastric SRCC exhibited lower concentrations of CEA (P < .001) and CA19-9 (P = .002), along with reduced positive rates of CEA (P = .041), CA19-9 (P = .003), AFP (P < .001), and CA242 (P = .006), while displaying higher positive rates of CA724 (P = .024) than gastric adenocarcinoma. Nevertheless, the receiver operating characteristic curve demonstrated that serum tumor markers did not hold clinical significance in differentiating between gastric adenocarcinoma and SRCC. Survival analysis substantiated that the combined criteria of serum tumor markers stood as an independent risk factor for both gastric adenocarcinoma and SRCC. Notably, the nomogram indicated that serum tumor markers exerted a more substantial influence on the prognosis of gastric adenocarcinoma than on gastric SRCC. CONCLUSION: The study concluded that the combined criteria of serum tumor markers emerge as independent risk factors for both subtypes of gastric cancer. Furthermore, this combined approach exhibited enhanced efficacy in prognosticating the outcome of gastric adenocarcinoma compared with gastric SRCC.

Clinicopathological characteristics of gastric neuroendocrine neoplasms: A comprehensive analysis.

OBJECTIVE: This study aimed to explore the clinicopathological characteristics and prognostic implications of gastric neuroendocrine neoplasms (g-NENs). METHODS: A retrospective enrollment of 142 patients diagnosed with g-NENs was conducted at Zhejiang Cancer Hospital between January 1, 2007 and December 31, 2021. The study compared essential clinicopathological features and survival rates. Additionally, the prognosis of gastric neuroendocrine carcinomas/mixed neuroendocrine-non-neuroendocrine neoplasms (g-NEC/MiNEN) were contrasted with those of gastric adenocarcinoma (GAC) and signet ring cell carcinoma (SRCC). RESULTS: The study comprised a total of 142 g-NENs cases, with a male-to-female ratio of approximately 2:1. The 5-year survival rates for g-NEC and g-MiNEN were 26.7% and 35.2%, respectively. Corresponding 5-year survival rates for G1 and G2 were observed at 100% and 80.0%, respectively. g-NEC/MiNEN showed a significantly worse prognosis compared to g-NET (p < 0.001). g-NEC/MiNEN exhibited a poor prognosis compared to GAC (p < 0.001), and within poorly differentiated GAC, g-NEC/MiNEN demonstrated a worse prognosis (p = 0.007). Additionally, patients receiving postoperative adjuvant therapy exhibited notably prolonged overall survival (OS) in the case of g-NEC/MiNEN (p = 0.010). CONCLUSION: In short, the prognosis of g-NEC/MiNEN was worse than that of g-NET, GAC and poorly differentiated GAC, but this group benefit from postoperative adjuvant therapy.

A Novel Quercetin Encapsulated Glucose Modified Liposome and Its Brain-Target Antioxidative Neuroprotection Effects.

Neurodegenerative diseases (NDDs) are mainly induced by oxidative stress which produces excessive reactive oxygen species (ROS). Quercetin (QU) is a potent antioxidant with some effects on NDDs. This study prepared and characterized a novel glucose-modified QU liposome (QU-Glu-Lip), aiming not only to overcome QU's poor water solubility and bioavailability but also to deliver more QU to brain tissue to enhance its neuroprotective effect. QU-Glu-Lip possessed encapsulation efficiency (EE) of 89.9%, homogenous particle sizes (116-124 nm), small PDI value (<0.3), zeta value -1.363 ± 0.437 mV, proper pH and salt stability, and proper cytotoxicity. The glucose-modified liposome penetrated the blood-brain barrier (BBB) mediated via the glucose transporter 1 (GLUT1) and was taken by neuronal cells more efficiently than liposome without glucose, according to bEnd.3 and PC12 cell tests. QU-Glu-Lip attenuated H2O2-induced oxidative damage to PC12 with higher cell viability (88.42%) and lower intracellular ROS compared to that of QU. QU-Glu-Lip had higher brain target ability and delivered more QU to neuronal cells, effectively exerting the antioxidative neuroprotection effect. There is potential for the QU-Glu-Lip application for more effective treatment of NDDs.

Juvenile hormone inhibits adult cuticle formation in Drosophila melanogaster through Kr-h1/Dnmt2-mediated DNA methylation of Acp65A promoter.

Differentiation of imaginal epidermal cells of Drosophila melanogaster to form adult cuticles occurs at approximately 40-93 h after puparium formation. Juvenile hormone (JH) given at pupariation results in formation of a second pupal cuticle in the abdomen instead of the adult cuticle. Although the adult cuticle gene Acp65A has been reported to be down-regulated following JH treatment, the regulatory mechanism remains unclear. Here, we found that the JH primary response gene Krüppel homologue 1 (Kr-h1) plays a vital role in the repression of adult cuticle formation through the mediation of JH action. Overexpression of Kr-h1 mimicked-while knocking down of Kr-h1 attenuated-the inhibitory action of JH on the formation of the adult abdominal cuticle. Further, we found that Kr-h1 inhibited the transcription of Acp65A by directly binding to the consensus Kr-h1 binding site (KBS) within the Acp65A promoter region. Moreover, the DNA methyltransferase Dnmt2 was shown to interact with Kr-h1, combined with the KBS to promote the DNA methylation of sequences around the KBS, in turn inhibiting the transcription of Acp65A. This study advances our understanding of the molecular basis of the "status quo" action of JH on the Drosophila adult metamorphosis.

Research progress of hexokinase 2 in inflammatory-related diseases and its inhibitors.

Hexokinase 2 (HK2) is a crucial enzyme involved in glycolysis, which converts glucose into glucose-6-phosphate and plays a significant role in glucose metabolism. HK2 can mediate glycolysis, which is linked to the release of inflammatory factors. The over-expression of HK2 increases the production of pro-inflammatory cytokines, exacerbating the inflammatory reaction. Consequently, HK2 is closely linked to various inflammatory-related diseases affecting multiple systems, including the digestive, nervous, circulatory, respiratory, reproductive systems, as well as rheumatoid arthritis. HK2 is regarded as a novel therapeutic target for inflammatory-related diseases, and this article provides a comprehensive review of its roles in these conditions. Furthermore, the development of potent HK2 inhibitors has garnered significant attention in recent years. Therefore, this review also presents a summary of potential HK2 inhibitors, offering promising prospects for the treatment of inflammatory-related diseases in the future.

A correlation analysis on the postpartum anxiety disorder and influencing factors in puerperae with gestational diabetes mellitus.

Objective: The aim of this study is to discuss the postpartum anxiety disorder and influencing factors in puerperae with gestational diabetes mellitus (GDM) to provide a clinical basis for better early identification and intervention of adverse mood. Methods: Convenient sampling method was adopted to investigate 205 pregnant women as the observation group and 201 normal healthy pregnant women in the same period as the control group. The self-rating anxiety scale (SAS) was used to investigate and observe the respondents, evaluate the postpartum anxiety status of patients with GDM, and analyze the related influencing factors. Statistical analysis of the data was performed using SAS 3.0 software. A proposed P < 0.05 was considered as statistically significant. Results: Patients with GDM had a higher risk than normal maternal anxiety, related to years of education, triglycerides, 1-h postprandial blood glucose, and a history of induced abortion. Conclusion: GDM can lead to the occurrence of postpartum anxiety, and the poor psychological state is not conducive to the maternal and infant health. Early identification and early intervention can reduce the harm caused by anxiety and promote the progress of maternal and infant health and clinical research.

Nectin-4 has emerged as a compelling target for breast cancer.

The incidence of breast cancer in women has increased year by year, becoming one of the most common malignant tumors in females worldwide. Most patients can be treated with surgery and endocrine drugs, but there are still some patients who lack effective treatment, such as triple-negative breast cancer (TNBC). Nectin-4, a protein encoded by poliovirus receptor-associated protein 4, is a Ca2+-independent immunoglobulin-like protein. It is mainly involved in the adhesion between cells. In recent years, studies have found that Nectin-4 is overexpressed in breast cancer and several other malignancies. Otherwise, several monoclonal antibodies and inhibitors targeting Nectin-4 have shown prosperous outcomes, so Nectin-4 has great potential to be a therapeutic target for breast cancer. The present review systematically describes the significance of Nectin-4 in each aspect of breast cancer, as well as the molecular mechanisms of these aspects mediated by Nectin-4. We further highlight ongoing or proposed therapeutic strategies for breast cancer specific to Nectin-4.

The Impact of a Humanized Nursing Model on the Nursing Outcomes of Emergency Transfusion Patients.

Background: Emergency transfusion is a frequently performed invasive medical procedure. Patients often experience negative emotions and exhibit poor compliance during transfusion. Therefore, it is imperative to proactively implement effective nursing interventions. Objective: This study aims to investigate the impact of a humanized nursing model on the nursing outcomes of emergency transfusion patients. Design: This research was conducted as a randomized controlled experiment. Setting: The study was conducted in the emergency department of Suzhou Hospital of Integrated Chinese and Western Medicine. Participants: A total of 120 patients who underwent emergency transfusion treatment in our hospital from February 2021 to October 2022 were selected. They were divided into two groups, the control group, and the observation group, using a random number table method, with 60 patients in each group. Interventions: The control group received standard nursing care, while the observation group received humanized nursing. Primary Outcome Measures: The primary outcome measures included (1) assessment of psychological states, (2) evaluation of physical and mental comfort, (3) assessment of transfusion compliance, (4) incidence of adverse transfusion events, and (5) assessment of nursing satisfaction. Results: Prior to nursing interventions, anxiety and depression scores were not significantly different between the two groups (P > .05). After nursing interventions, both groups exhibited a decrease in scores, with the observation group showing a more significant reduction compared to the control group (P < .05). In all aspects of physical and mental comfort, the observation group scored significantly higher than the control group (P < .05). Transfusion compliance and nursing satisfaction were significantly higher in the observation group compared to the control group (P < .01). The incidence of adverse transfusion events in the observation group was significantly lower than in the control group (P < .01). Conclusions: Humanized nursing significantly improves anxiety and depression in emergency transfusion patients, enhances their physical and mental comfort, and increases transfusion compliance while reducing adverse transfusion events. It leads to high patient satisfaction with nursing services.

Comparison of Clinicopathological Features and Prognosis of Mucinous Gastric Carcinoma and other Gastric Cancers: A Retrospective Study of 4,417 Patients.

BACKGROUND: Mucinous gastric carcinoma (MGC) is a distinct histologic subtype of gastric cancer (GC) that is often diagnosed at an advanced stage. The clinicopathological characteristics and prognosis of MGC, when compared to adenocarcinoma and signet-ring cell carcinoma (SRCC), are currently subjects of debate and require further investigation. METHODS: In this study, we conducted an investigation on 4,417 patients who were hospitalized with GC at Zhejiang Cancer Hospital between April 2008 and December 2019. The objective was to compare the prognosis and clinicopathological characteristics of MGC with other types of GC. RESULTS: In comparison to adenocarcinoma, MGC patients exhibited more advanced tumor infiltration (p < 0.001), lower tumor differentiation (p < 0.001), and higher rates of preoperative tumor marker positivity (except for AFP and CA125) (all p < 0.05). However, after propensity score matching (PSM) to eliminate confounding factors, MGC patients surprisingly exhibited a better prognosis than adenocarcinoma patients (p = 0.008), and the results in multifactorial COX regression were similar (HR = 0.792, 95% CI 0.629-0.997, p = 0.047). Among patients with MGC, age, pN stage, as well as preoperative levels of CA125 and CA724 (all p < 0.05), emerged as independent prognostic markers. While overall survival did not significantly differ between MGC and SRCC (p = 0.196), significant survival disparities emerged in advanced-stage patients (p = 0.009), with MGC showing better survival rates. Furthermore, a nomogram was developed to predict 1-, 3-, and 5-year survival in gastric cancer patients based on various factors, achieving a C-index of 0.772 (95% CI: 0.745-0.799). CONCLUSIONS: While the poorer prognosis associated with MGC may be linked to its advanced stage and lower degree of differentiation, its biological behavior could contribute to improved survival.

Role and mechanisms of SGLT-2 inhibitors in the treatment of diabetic kidney disease.

Diabetic kidney disease (DKD) is a chronic inflammatory condition that affects approximately 20-40% of individuals with diabetes. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors, emerging as novel hypoglycemic agents, have demonstrated significant cardiorenal protective effects in patients with DKD. Initially, it was believed that the efficacy of SGLT-2 inhibitors declined as the estimated glomerular filtration rate (eGFR) decreased, which led to their preferential use in DKD patients at G1-G3 stages. However, recent findings from the DAPA-CKD and EMPA-KIDNEY studies have revealed equally beneficial cardiorenal effects of SGLT-2 inhibitors in individuals at stage G4 DKD, although the underlying mechanism behind this phenomenon remains unclear. In this comprehensive analysis, we provide a systematic review of the mechanisms and functioning of SGLT-2 inhibitors, potential renal protection mechanisms, and the therapeutic efficacy and safety of SGLT-2 inhibitors in kidney diseases, with a particular focus on stage G4 DKD. Gaining a deeper understanding of the renal protective effect of SGLT-2 inhibitors and their underlying mechanisms is highly significance for the successful utilization of these inhibitors in the treatment of diverse kidney disorders.

Sociodemographic features associated with the MoCA, SPPB, and GDS scores in a community-dwelling elderly population.

BACKGROUND: An accurate evaluation of cognitive function, physical health, and psychological health is fundamental for assessing health problems in the elderly population, and it is important to identify the necessity of early therapeutic intervention. The objective of this study was to evaluate the states of mental and physical functions and to investigate the relationships between sociodemographic features and these functions in a community-dwelling elderly population. METHODS: This community-based cross-sectional study was conducted in a suburban district of Shanghai, China. A total of 1025 participants aged 60-89 years underwent investigations of demographic and lifestyle features and a multidimensional geriatric evaluation comprising the Montreal Cognitive Assessment (MoCA), Short Physical Performance Battery (SPPB), and Geriatric Depression Scale (GDS). RESULTS: The results of the multivariate linear regression models demonstrated that the MoCA and SPPB scores decreased with advancing age (all P < 0.01). However, the GDS score did not exhibit an age-related decrease (P = 0.09). Both sex and living alone influenced the MoCA score (P < 0.01 and P = 0.04, respectively), SPPB score (P < 0.01 and P = 0.04, respectively), and GDS score (P < 0.01 and P < 0.01, respectively). A higher education level was related to better MoCA and SPPB scores (all P < 0.01). Furthermore, age and sex had interactive effects on the MoCA score (P = 0.03) and SPPB score (P < 0.01). The kernel-weighted local polynomial smoothing curves exhibited similar trends. CONCLUSIONS: It is imperative to develop a more sensitive evaluation of physical function, and to encourage various intellectually and emotionally stimulating social activity strategies to promote healthy aging, especially in elderly women and those living alone who have a low education level.

The percentages of signet-ring cells (SRCs) affects the prognosis after radical gastrectomy for advanced gastric cancer.

PURPOSE: Only recently has the percentage of signet-ring cells (SRCs) been shown to affect the prognosis following gastric cancer surgery. It is uncertain whether the SRC percentage has a role in tumour biology or prognosis of gastric signet-ring cell carcinoma (GSRCC). For this research, we assessed the effect of the SRC percentage on the clinicopathological and prognostic characteristics of gastric cancer (GC) tumours and created and verified a prognostic nomogram to assess the overall survival (OS) of GSRCC patients. METHODS: In our study, 1100 GC patients with signet-ring cell carcinoma (SRCC) at Zhejiang Cancer Hospital from December 2013 to December 2018 who underwent curative gastric cancer resection were retrospectively analysed. The patients were separated into two groups: those with SRCC (SRC percentage >50%; n = 157) and those with partial signet-ring cell carcinoma (PSRCC) (SRC percentage ≤50%; n = 943). We compared the clinicopathological characteristics of both groups. To estimate OS and determine correlations with the SRC percentage, the Kaplan-Meier method and log-rank test were used. To develop the prognostic nomogram, independent prognostic indicators for OS were identified using Cox regression analyses. Predictions were assessed using the calibration curve and C-index. RESULTS: Our research showed that there was no discernible difference in OS between the two groups. The preoperative CA242 level, pT stage, pN stage, age, nerve invasion, neoadjuvant chemotherapy, postoperative chemotherapy, and maximum tumour diameter were independent prognostic risk factors for OS for GC (all p < 0.05). However, for advanced GC, the SRC percentage (HR = 1.571, 95% CI 1.072-2.302, p = 0.020) was an independent prognostic factor of OS. Other independent prognostic risk factors were age, pT stage, pN stage, nerve invasion, tumour location, neoadjuvant chemotherapy, postoperative chemotherapy, preoperative CA50 level, and preoperative CEA level (all p < 0.05). On these bases, nomograms were constructed for GC and advanced GC, with C-indexes of 0.806 (95%CI 0.782-0.830) and 0.728 (95%CI 0.697-0.759), respectively. CONCLUSIONS: In cases of advanced gastric cancer, the SRC percentage served as a standalone prognostic indicator for OS. An effective tool for assessing the prognosis of GSRCC was offered by the nomogram.